Inactive alleles of cytochrome P450 2C19 may be positively selected in human evolution Genome evolution and evolutionary systems biology

© 2014 Janha et al.; licensee BioMed Central Ltd.Background: Cytochrome P450 CYP2C19 metabolizes a wide range of pharmacologically active substances and a relatively small number of naturally occurring environmental toxins. Poor activity alleles of CYP2C19 are very frequent worldwide, particularly in Asia, raising the possibility that reduced metabolism could be advantageous in some circumstances. The evolutionary selective forces acting on this gene have not previously been investigated. We analyzed CYP2C19 genetic markers from 127 Gambians and on 120 chromosomes from Yoruba, Europeans and Asians (Japanese + Han Chinese) in the Hapmap database. Haplotype breakdown was explored using bifurcation plots and relative extended haplotype homozygosity (REHH). Allele frequency differentiation across populations was estimated using the fixation index (FST) and haplotype diversity with coalescent models. Results: Bifurcation plots suggested conservation of alleles conferring slow metabolism (CYP2C19∗2 and ∗3). REHH was high around CYP2C19∗2 in Yoruba (REHH 8.3, at 133.3 kb from the core) and to a lesser extent in Europeans (3.5, at 37.7 kb) and Asians (2.8, at -29.7 kb). FST at the CYP2C19 locus was low overall (0.098). CYP2C19∗3 was an FST outlier in Asians (0.293), CYP2C19 haplotype diversity ST is low at the CYP2C19 locus, suggesting balancing selection overall. The biological factors responsible for these selective pressures are currently unknown. One possible explanation is that early humans were exposed to a ubiquitous novel toxin activated by CYP2C19. The genetic adaptation took place within the last 10,000 years which coincides with the development of systematic agricultural practices.This work was supported by the Medical Research Council Unit The Gambia and the European and Developing Countries Clinical Trials Partnership [grant number CG_ta_05_40204_018]

Once a pond in time: employing palaeoecology to inform farmland pond restoration

The restoration of highly terrestrialized farmland ponds that combines the removal of woody vegetation and pond sediment greatly enhances aquatic biodiversity. Nonetheless, questions remain regarding the historical precedent of pond restoration, and particularly if post-restoration aquatic macrophyte communities resemble pre-terrestrialization assemblages. We used a paleoecological approach to address these questions for a typical, recently restored farmland pond in Norfolk, eastern England. Plant and animal remains in pond sediment cores were used to infer decadal-centennial scale changes to pond communities and to identify past pond management events. We then evaluated the resemblance of restored and historical assemblages by comparisons with contemporary post-restoration vegetation data. Based on changes in the abundance of terrestrial leaf remains and other indicators (increases followed by declines of aquatic organisms), the study pond appears to have a long history (going back to the early-1800s) of canopy management (at least three inferred management events), but after the mid-1970s, steady and substantial increases in terrestrial indicators, suggest cessation of management resulting in uninterrupted terrestrialization. Aquatic macrophyte communities arising after restoration showed some similarities with historical assemblages, but also contained apparently new species. This study demonstrates how paleolimnological methods can improve understanding of pond ecological histories to better inform restoration targets and practices. Implications for Practice Paleolimnological methods can be successfully employed at small, human-made ponds to assess past biological communities and trajectories of ecological change. Restoration of heavily terrestrialized farmland ponds through major woody vegetation and sediment removal mimics periodic management activities undertaken over past centuries and is essential to the maintenance of open canopy conditions and biodiversity conservation. Caution must be taken when setting restoration targets for farmland ponds as rare macrophyte species indicative of high water quality may not necessarily return to restored pond habitats due to fragmentation effects associated with the loss of local populations and/or in-pond eutrophication development

Nocturnal pollinators strongly contribute to pollen transport of wild flowers in an agricultural landscape

Dramatic declines in diurnal pollinators have created great scientific interest in plant–pollinator relationships and associated pollination services. Existing literature, however, is generally focused on diurnal pollinating insect taxa, especially on Apidae (Hymenoptera) and Syrphidae (Diptera) pollinators, while nocturnal macro-moths that comprise extremely species-rich flower-visiting families have been largely neglected. Here, we report that in agricultural landscapes, macro-moths can provide unique, highly complex pollen transport links, making them vital components of overall wild plant–pollinator networks in agro-ecosystems. Pollen transport occurred more frequently on the moths' ventral thorax rather than on their mouthparts that have been traditionally targeted for pollen swabbing. Pollen transport loads suggest that nocturnal moths contribute key pollination services for several wild plant families in agricultural landscapes, in addition to providing functional resilience to diurnal networks. Severe declines in richness and abundance of settling moth populations highlight the urgent need to include them in future management and conservation strategies within agricultural landscapes

Improving the pollinator pantry: Restoration and management of open farmland ponds enhances the complexity of plant-pollinator networks

In line with general biodiversity losses across agricultural landscapes, insect pollinators have experienced recent sharp declines. A range of conservation measures have been developed to address these declines, with plant-pollinator interaction networks providing key insights into the effectiveness of these measures. For the first time, we studied interactions between three diurnal pollinator groups (bees, hoverflies, and butterflies) and insect-pollinated plants to understand how they are affected by pond management and restoration. Major network contributors were identified, and important network-level parameters compared at nine farmland ponds under different management strategies to assess management effects on plant-pollinator interactions: three ‘overgrown’ tree-covered ponds, three ‘long-term managed ponds’ kept in an open-canopy, early- to mid-successional state by periodic interventions involving tree and sediment removal, and three ‘recently restored ponds’, initially heavily overgrown with woody vegetation, and subsequently rapidly transformed into an early succession state through major tree and sediment removal. Interaction complexity, as measured by the metrics ‘links per species’, ‘linkage density’, Fisher’s alpha and Shannon’s Diversity, was higher for both long-term managed and recently restored ponds compared to overgrown ponds. Several network-level parameters indicated that highest complexity levels were found at recently restored ponds due to their substantially higher plant diversity. Bipartite interaction analysis suggests major benefits of pond management and restoration for agricultural pollinator assemblages. We strongly advocate the inclusion of ponds in conservation strategies and policies aimed at pollinators - ponds should be part of the pollinator pantry

Nasal Lipopolysaccharide Challenge and Cytokine Measurement Reflects Innate Mucosal Immune Responsiveness

<div><p>Background</p><p><b>P</b>ractical methods of monitoring innate immune mucosal responsiveness are lacking. Lipopolysaccharide (LPS) is a component of the cell wall of Gram negative bacteria and a potent activator of Toll-like receptor (TLR)-4. To measure LPS responsiveness of the nasal mucosa, we administered LPS as a nasal spray and quantified chemokine and cytokine levels in mucosal lining fluid (MLF).</p><p>Methods</p><p>We performed a 5-way cross-over, single blind, placebo-controlled study in 15 healthy non-atopic subjects (n = 14 <i>per protocol</i>). Doses of ultrapure LPS (1, 10, 30 or 100μg/100μl) or placebo were administered by a single nasal spray to each nostril. Using the recently developed method of nasosorption with synthetic adsorptive matrices (SAM), a series of samples were taken. A panel of seven cytokines/chemokines were measured by multiplex immunoassay in MLF. mRNA for intercellular cell adhesion molecule-1 (ICAM-1) was quantified from nasal epithelial curettage samples taken before and after challenge.</p><p>Results</p><p>Topical nasal LPS was well tolerated, causing no symptoms and no visible changes to the nasal mucosa. LPS induced dose-related increases in MLF levels of IL-1β, IL-6, CXCL8 (IL-8) and CCL3 (MIP-1α) (AUC at 0.5 to 10h, compared to placebo, p<0.05 at 30 and 100μg LPS). At 100μg LPS, IL-10, IFN-α and TNF-α were also increased (p<0.05). Dose-related changes in mucosal ICAM-1 mRNA were also seen after challenge, and neutrophils appeared to peak in MLF at 8h. However, 2 subjects with high baseline cytokine levels showed prominent cytokine and chemokine responses to relatively low LPS doses (10μg and 30μg LPS).</p><p>Conclusions</p><p>Topical nasal LPS causes dose-dependent increases in cytokines, chemokines, mRNA and cells. However, responsiveness can show unpredictable variations, possibly because baseline innate tone is affected by environmental factors. We believe that this new technique will have wide application in the study of the innate immune responses of the respiratory mucosa.</p><p>Key Messages</p><p>Ultrapure LPS was used as innate immune stimulus in a human nasal challenge model, with serial sampling of nasal mucosal lining fluid (MLF) by nasosorption using a synthetic absorptive matrix (SAM), and nasal curettage of mucosal cells. A dose response could be demonstrated in terms of levels of IL-1β, IL-6, CXCL8 and CCL3 in MLF, as well as ICAM-1 mRNA in nasal curettage specimens, and levels of neutrophils in nasal lavage. Depending on higher baseline levels of inflammation, there were occasional magnified innate inflammatory responses to LPS.</p><p>Trial Registration</p><p>Clinical Trials.gov <a href="https://clinicaltrials.gov/ct2/show/NCT02284074?term=nasal+lipopolysaccharide&rank=1" target="_blank">NCT02284074</a></p></div

The incidence of total hip arthroplasty after hip arthroscopy in osteoarthritic patients

<p>Abstract</p> <p>Objective</p> <p>To assess the incidence of total hip arthroplasty (THA) in osteoarthritic patients who were treated by arthroscopic debridement and to evaluate factors that might influence the time interval from the first hip arthroscopy to THA.</p> <p>Design</p> <p>Retrospective clinical series</p> <p>Methods</p> <p>Follow-up data and surgical reports were retrieved from 564 records of osteoarthritic patients that have had hip arthroscopy between the years 2002 to 2009 with a mean follow-up time of 3.2 years (range, 1-6.4 years). The time interval between the first hip arthroscopy to THA was modelled as a function of patient age; level of cartilage damage; procedures performed and repeated arthroscopies with the use of multivariate regression analysis.</p> <p>Results</p> <p>Ninety (16%) of all participants eventually required THA. The awaiting time from the first arthroscopy to a hip replacement was found to be longer in patients younger than 55 years and in a milder osteoarthritic stage. Patients that experienced repeated hip scopes had a longer time to THA than those with only a single procedure. Procedures performed concomitant with debridement and lavage did not affect the time interval to THA.</p> <p>Conclusions</p> <p>In our series of arthroscopic treatment of hip osteoarthritis, 16% required THA over a period of 7 years. Factors that influence the time to arthroplasty were age, degree of osteoarthritis and recurrent procedures.</p

Predicting the start week of respiratory syncytial virus outbreaks using real time weather variables

<p>Abstract</p> <p>Background</p> <p>Respiratory Syncytial Virus (RSV), a major cause of bronchiolitis, has a large impact on the census of pediatric hospitals during outbreak seasons. Reliable prediction of the week these outbreaks will start, based on readily available data, could help pediatric hospitals better prepare for large outbreaks.</p> <p>Methods</p> <p>Naïve Bayes (NB) classifier models were constructed using weather data from 1985-2008 considering only variables that are available in real time and that could be used to forecast the week in which an RSV outbreak will occur in Salt Lake County, Utah. Outbreak start dates were determined by a panel of experts using 32,509 records with ICD-9 coded RSV and bronchiolitis diagnoses from Intermountain Healthcare hospitals and clinics for the RSV seasons from 1985 to 2008.</p> <p>Results</p> <p>NB models predicted RSV outbreaks up to 3 weeks in advance with an estimated sensitivity of up to 67% and estimated specificities as high as 94% to 100%. Temperature and wind speed were the best overall predictors, but other weather variables also showed relevance depending on how far in advance the predictions were made. The weather conditions predictive of an RSV outbreak in our study were similar to those that lead to temperature inversions in the Salt Lake Valley.</p> <p>Conclusions</p> <p>We demonstrate that Naïve Bayes (NB) classifier models based on weather data available in real time have the potential to be used as effective predictive models. These models may be able to predict the week that an RSV outbreak will occur with clinical relevance. Their clinical usefulness will be field tested during the next five years.</p

Defecting or not defecting: how to "read" human behavior during cooperative games by EEG measurements

Understanding the neural mechanisms responsible for human social interactions is difficult, since the brain activities of two or more individuals have to be examined simultaneously and correlated with the observed social patterns. We introduce the concept of hyper-brain network, a connectivity pattern representing at once the information flow among the cortical regions of a single brain as well as the relations among the areas of two distinct brains. Graph analysis of hyper-brain networks constructed from the EEG scanning of 26 couples of individuals playing the Iterated Prisoner's Dilemma reveals the possibility to predict non-cooperative interactions during the decision-making phase. The hyper-brain networks of two-defector couples have significantly less inter-brain links and overall higher modularity - i.e. the tendency to form two separate subgraphs - than couples playing cooperative or tit-for-tat strategies. The decision to defect can be "read" in advance by evaluating the changes of connectivity pattern in the hyper-brain network

Organisational participation and women - an attitude problem?

Employee participation is a dynamic and contested area of organisational behaviour, attracting continuing academic, practitioner and policy interest and debate. This chapter focuses on organisational participation and women