Adaptive Evolution of Escherichia coli to an α-Peptide/β-Peptoid Peptidomimetic Induces Stable Resistance.

Antimicrobial peptides (AMPs) and synthetic analogues thereof target conserved structures of bacterial cell envelopes and hence, development of resistance has been considered an unlikely event. However, recently bacterial resistance to AMPs has been observed, and the aim of the present study was to determine whether bacterial resistance may also evolve against synthetic AMP analogues, e.g. α-peptide/β-peptoid peptidomimetics. E. coli ATCC 25922 was exposed to increasing concentrations of a peptidomimetic (10 lineages), polymyxin B (10 lineages), or MilliQ water (4 lineages) in a re-inoculation culturing setup covering approx. 500 generations. All 10 lineages exposed to the peptidomimetic adapted to 32 × MIC while this occurred for 8 out of 10 of the polymyxin B-exposed lineages. All lineages exposed to 32 × MIC of either the peptidomimetic or polymyxin B had a significantly increased MIC (16-32 ×) to the selection agent. Five transfers (≈ 35 generations) in unsupplemented media did not abolish resistance indicating that resistance was heritable. Single isolates from peptidomimetic-exposed lineage populations displayed MICs against the peptidomimetic from wild-type MIC to 32 × MIC revealing heterogeneous populations. Resistant isolates showed no cross-resistance against a panel of membrane-active AMPs. These isolates were highly susceptible to blood plasma antibacterial activity and were killed when plasma concentrations exceeded ≈ 30%. Notably, MIC of the peptidomimetic against resistant isolates returned to wild-type level upon addition of 25% plasma. Whole-genome sequencing of twenty isolates from four resistant lineages revealed mutations, in murein transglycosylase D (mltD) and outer-membrane proteins, which were conserved within and between lineages. However, no common resistance-conferring mutation was identified. We hypothesise that alterations in cell envelope structure result in peptidomimetic resistance, and that this may occur via several distinct mechanisms. Interestingly, this type of resistance result in a concomitant high susceptibility towards plasma, and therefore the present study does not infer additional concern for peptidomimetics as future therapeutics

Comparative effect of intraoperative propacetamol versus placebo on morphine consumption after elective reduction mammoplasty under remifentanil-based anesthesia: a randomized control trial [ISRCTN71723173]

BACKGROUND: Postoperative administration of paracetamol or its prodrug propacetamol has been shown to decrease pain with a morphine sparing effect. However, the effect of propacetamol administered intra-operatively on post-operative pain and early postoperative morphine consumption has not been clearly evaluated. In order to evaluate the effectiveness of analgesic protocols in the management of post-operative pain, a standardized anesthesia protocol without long-acting opioids is crucial. Thus, for ethical reasons, the surgical procedure under general anesthesia with remifentanil as the only intraoperative analgesic must be associated with a moderate predictable postoperative pain. METHODS: We were interested in determining the postoperative effect of propacetamol administered intraoperatively after intraoperative remifentanil. Thirty-six adult women undergoing mammoplasty with remifentanil-based anesthesia were randomly assigned to receive propacetamol 2 g or placebo one hour before the end of surgery. After remifentanil interruption and tracheal extubation in recovery room, pain was assessed and intravenous titrated morphine was given. The primary end-point was the cumulative dose of morphine administered in the recovery room. The secondary end-points were the pain score after tracheal extubation and one hour after, the delay for obtaining a Simplified Numerical Pain Scale (SNPS) less than 4, and the incidence of morphine side effects in the recovery room. For intergroup comparisons, categorical variables were compared using the chi-squared test and continuous variables were compared using the Student t test or Mann-Whitney U test, as appropriate. A p value less than 0.05 was considered as significant. RESULTS: In recovery room, morphine consumption was lower in the propacetamol group than in the placebo group (p = 0.01). Pain scores were similar in both groups after tracheal extubation and lower in the propacetamol group (p = 0.003) one hour after tracheal extubation. The time to reach a SNPS < 4 was significantly shorter in the propacetamol group (p = 0.02). The incidence of morphine related side effects did not differ between the two groups. CONCLUSIONS: Intraoperative propacetamol administration with remifentanil based-anesthesia improved significantly early postoperative pain by sparing morphine and shortening the delay to achieve pain relief

Wheat TaRab7 GTPase Is Part of the Signaling Pathway in Responses to Stripe Rust and Abiotic Stimuli

Small GTP-binding proteins function as regulators of specific intercellular fundamental biological processes. In this study, a small GTP-binding protein Rab7 gene, designated as TaRab7, was identified and characterized from a cDNA library of wheat leaves infected with Puccinia striiformis f. sp. tritici (Pst) the wheat stripe rust pathogen. The gene was predicted to encode a protein of 206 amino acids, with a molecular mass of 23.13 KDa and an isoeletric point (pI) of 5.13. Further analysis revealed the presence of a conserved signature that is characteristic of Rab7, and phylogenetic analysis demonstrated that TaRab7 has the highest similarity to a small GTP binding protein gene (BdRab7-like) from Brachypodium distachyon. Quantitative real-time PCR assays revealed that the expression of TaRab7 was higher in the early stage of the incompatible interactions between wheat and Pst than in the compatible interaction, and the transcription level of TaRab7 was also highly induced by environmental stress stimuli. Furthermore, knocking down TaRab7 expression by virus induced gene silencing enhanced the susceptibility of wheat cv. Suwon 11 to an avirulent race CYR23. These results imply that TaRab7 plays an important role in the early stage of wheat-stripe rust fungus interaction and in stress tolerance

Migrant birds and mammals live faster than residents

Billions of vertebrates migrate to and from their breeding grounds annually, exhibiting astonishing feats of endurance. Many such movements are energetically costly yet there is little consensus on whether or how such costs might influence schedules of survival and reproduction in migratory animals. Here we provide a global analysis of associations between migratory behaviour and vertebrate life histories. After controlling for latitudinal and evolutionary patterns, we find that migratory birds and mammals have faster paces of life than their non-migratory relatives. Among swimming and walking species, migrants tend to have larger body size, while among flying species, migrants are smaller. We discuss whether pace of life is a determinant, consequence, or adaptive outcome, of migration. Our findings have important implications for the understanding of the migratory phenomenon and will help predict the responses of bird and mammal species to environmental changeinfo:eu-repo/semantics/publishedVersio

Habitat and forage associations of a naturally colonising insect pollinator, the Tree Bumblebee Bombus hypnorum

Bumblebees (Bombus species) are major pollinators of commercial crops and wildflowers but factors affecting their abundance, including causes of recent population declines, remain unclear. Investigating the ecology of species with expanding ranges provides a potentially powerful means of elucidating these factors. Such species may also bring novel pollination services to their new ranges. We therefore investigated landscape-scale habitat use and foraging preferences of the Tree Bumblebee, B. hypnorum, a recent natural colonist that has rapidly expanded its range in the UK over the past decade. Counts of B. hypnorum and six other Bombus species were made in March-June 2012 within a mixed landscape in south-eastern Norfolk, UK. The extent of different landscape elements around each transect was quantified at three scales (250 m, 500 m and 1500 m). We then identified the landscape elements that best predicted the density of B. hypnorum and other Bombus species. At the best fitting scale (250 m), B. hypnorum density was significantly positively associated with extent of both urban and woodland cover and significantly negatively associated with extent of oilseed rape cover. This combination of landscape predictors was unique to B. hypnorum. Urban and woodland cover were associated with B. hypnorum density at three and two, respectively, of the three scales studied. Relative to other Bombus species, B. hypnorum exhibited a significantly higher foraging preference for two flowering trees, Crataegus monogyna and Prunus spinosa, and significantly lower preferences for Brassica napus, Glechoma hederacea and Lamium album. Our study provides novel, quantitative support for an association of B. hypnorum with urban and woodland landscape elements. Range expansion in B. hypnorum appears to depend, on exploitation of widespread habitats underutilised by native Bombus species, suggesting B. hypnorum will readily co-exist with these species. These findings suggest that management could target bumblebee species with distinctive habitat requirements to help maintain pollination service

Glaciation Effects on the Phylogeographic Structure of Oligoryzomys longicaudatus (Rodentia: Sigmodontinae) in the Southern Andes

The long-tailed pygmy rice rat Oligoryzomys longicaudatus (Sigmodontinae), the major reservoir of Hantavirus in Chile and Patagonian Argentina, is widely distributed in the Mediterranean, Temperate and Patagonian Forests of Chile, as well as in adjacent areas in southern Argentina. We used molecular data to evaluate the effects of the last glacial event on the phylogeographic structure of this species. We examined if historical Pleistocene events had affected genetic variation and spatial distribution of this species along its distributional range. We sampled 223 individuals representing 47 localities along the species range, and sequenced the hypervariable domain I of the mtDNA control region. Aligned sequences were analyzed using haplotype network, Bayesian population structure and demographic analyses. Analysis of population structure and the haplotype network inferred three genetic clusters along the distribution of O. longicaudatus that mostly agreed with the three major ecogeographic regions in Chile: Mediterranean, Temperate Forests and Patagonian Forests. Bayesian Skyline Plots showed constant population sizes through time in all three clusters followed by an increase after and during the Last Glacial Maximum (LGM; between 26,000–13,000 years ago). Neutrality tests and the “g” parameter also suggest that populations of O. longicaudatus experienced demographic expansion across the species entire range. Past climate shifts have influenced population structure and lineage variation of O. longicaudatus. This species remained in refugia areas during Pleistocene times in southern Temperate Forests (and adjacent areas in Patagonia). From these refugia, O. longicaudatus experienced demographic expansions into Patagonian Forests and central Mediterranean Chile using glacial retreats

A Review of the Theoretical Basis, Effects, and Cost Effectiveness of Online Smoking Cessation Interventions in the Netherlands: A Mixed-Methods Approach

Background: Tobacco smoking is a worldwide public health problem. In 2015, 26.3% of the Dutch population aged 18 years and older smoked, 74.4% of them daily. More and more people have access to the Internet worldwide; approximately 94% of the Dutch population have online access. Internet-based smoking cessation interventions (online cessation interventions) provide an opportunity to tackle the scourge of tobacco. Objective: The goal of this paper was to provide an overview of online cessation interventions in the Netherlands, while exploring their effectivity, cost effectiveness, and theoretical basis. Methods: A mixed-methods approach was used to identify Dutch online cessation interventions, using (1) a scientific literature search, (2) a grey literature search, and (3) expert input. For the scientific literature, the Cochrane review was used and updated by two independent researchers (n=651 identified studies), screening titles, abstracts, and then full-text studies between 2013 and 2016 (CENTRAL, MEDLINE, and EMBASE). For the grey literature, the researchers conducted a Google search (n=100 websites), screening for titles and first pages. Including expert input, this resulted in six interventions identified in the scientific literature and 39 interventions via the grey literature. Extracted data included effectiveness, cost effectiveness, theoretical factors, and behavior change techniques used. Results: Overall, many interventions (45 identified) were offered. Of the 45 that we identified, only six that were included in trials provided data on effectiveness. Four of these were shown to be effective and cost effective. In the scientific literature, 83% (5/6) of these interventions included changing attitudes, providing social support, increasing self-efficacy, motivating smokers to make concrete action plans to prepare their attempts to quit and to cope with challenges, supporting identity change and advising on changing routines, coping, and medication use. In all, 50% (3/6) of the interventions included a reward for abstinence. Interventions identified in the grey literature were less consistent, with inclusion of each theoretical factor ranging from 31% to 67% and of each behavior change technique ranging from 28% to 54%. Conclusions: Although the Internet may provide the opportunity to offer various smoking cessation programs, the user is left bewildered as far as efficacy is concerned, as most of these data are not available nor offered to the smokers. Clear regulations about the effectiveness of these interventions need to be devised to avoid disappointment and failed quitting attempts. Thus, there is a need for policy regulations to regulate the proliferation of these interventions and to foster their quality in the Netherlands.Mir

Optimizing diffusion of an online computer tailored lifestyle program: a study protocol

ABSTRACT: Background Although the Internet is a promising medium to offer lifestyle interventions to large amounts of people at relatively low costs and effort, actual exposure rates of these interventions fail to meet the high expectations. Since public health impact of interventions is determined by intervention efficacy and level of exposure to the intervention, it is imperative to put effort in optimal dissemination. The present project attempts to optimize the dissemination process of a new online computer tailored generic lifestyle program by carefully studying the adoption process and developing a strategy to achieve sustained use of the program. Methods/Design A prospective study will be conducted to yield relevant information concerning the adoption process by studying the level of adoption of the program, determinants involved in adoption and characteristics of adopters and non-adopters as well as satisfied and unsatisfied users. Furthermore, a randomized control trial will be conducted to the test the effectiveness of a proactive strategy using periodic e-mail prompts in optimizing sustained use of the new program. Discussion Closely mapping the adoption process will gain insight in characteristics of adopters and non-adopters and satisfied and unsatisfied users. This insight can be used to further optimize the program by making it more suitable for a wider range of users, or to develop adjusted interventions to attract subgroups of users that are not reached or satisfied with the initial intervention. Furthermore, by studying the effect of a proactive strategy using period prompts compared to a reactive strategy to stimulate sustained use of the intervention and, possibly, behaviour change, specific recommendations on the use and the application of prompts in online lifestyle interventions can be developed. Trial registration Dutch Trial Register (NTR1786) and Medical Ethics Committee of Maastricht University and the University Hospital Maastricht (NL2723506809/MEC0903016)

Enhanced biological carbon consumption in a high CO2 ocean

The oceans have absorbed nearly half of the fossil-fuel carbon dioxide (CO2) emitted into the atmosphere since pre-industrial times1, causing a measurable reduction in seawater pH and carbonate saturation2. If CO2 emissions continue to rise at current rates, upper-ocean pH will decrease to levels lower than have existed for tens of millions of years and, critically, at a rate of change 100 times greater than at any time over this period3. Recent studies have shown effects of ocean acidification on a variety of marine life forms, in particular calcifying organisms4, 5, 6. Consequences at the community to ecosystem level, in contrast, are largely unknown. Here we show that dissolved inorganic carbon consumption of a natural plankton community maintained in mesocosm enclosures at initial CO2 partial pressures of 350, 700 and 1,050 μatm increases with rising CO2. The community consumed up to 39% more dissolved inorganic carbon at increased CO2 partial pressures compared to present levels, whereas nutrient uptake remained the same. The stoichiometry of carbon to nitrogen drawdown increased from 6.0 at low CO2 to 8.0 at high CO2, thus exceeding the Redfield carbon:nitrogen ratio of 6.6 in today’s ocean7. This excess carbon consumption was associated with higher loss of organic carbon from the upper layer of the stratified mesocosms. If applicable to the natural environment, the observed responses have implications for a variety of marine biological and biogeochemical processes, and underscore the importance of biologically driven feedbacks in the ocean to global change