699 research outputs found

    Determining the Repertoire of Immunodominant Proteins via Whole-Genome Amplification of Intracellular Pathogens

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    Culturing many obligate intracellular bacteria is difficult or impossible. However, these organisms have numerous adaptations allowing for infection persistence and immune system evasion, making them some of the most interesting to study. Recent advancements in genome sequencing, pyrosequencing and Phi29 amplification, have allowed for examination of whole-genome sequences of intracellular bacteria without culture. We have applied both techniques to the model obligate intracellular pathogen Anaplasma marginale and the human pathogen Anaplasma phagocytophilum, in order to examine the ability of phi29 amplification to determine the sequence of genes allowing for immune system evasion and long-term persistence in the host. When compared to traditional pyrosequencing, phi29-mediated genome amplification had similar genome coverage, with no additional gaps in coverage. Additionally, all msp2 functional pseudogenes from two strains of A. marginale were detected and extracted from the phi29-amplified genomes, highlighting its utility in determining the full complement of genes involved in immune evasion

    A phase I study of a new polyamine biosynthesis inhibitor, SAM486A, in cancer patients with solid tumours

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    Because tumour cell proliferation is highly dependent upon up-regulation of de-novo polyamine synthesis, inhibition of the polyamine synthesis pathway represents a potential target for anticancer therapy. SAM486A (CGP 48664) is a new inhibitor of the polyamine biosynthetic enzyme S-adenosylmethionine decarboxylase (SAMDC), more potent and specific than the first-generation SAMDC inhibitor methylglyoxal (bis) guanylhydrazone (MGBG). Preclinical testing confirmed promising antiproliferative activity. In this phase I study, SAM486A was given 4-weekly as a 120 h infusion. 39 adult cancer patients were enrolled with advanced/refractory disease not amenable to established treatments, PS ≤ 2, adequate marrow, liver, renal and cardiac function. Doses were escalated in 100% increments without toxicity in 24 pts from 3 mg m–2cycle–1up to 400 mg m–2cycle–1. At 550 and 700 mg m–2cycle–1reversible dose-limiting neutropenia occurred. Other toxicities included mild fatigue, nausea and vomiting. No objective remission was seen. Pharmakokinetic analysis showed a terminal half-life of approximately 2 days. AUC and Cmax were related to dose; neutropenia correlated with AUC. The recommended dose for further phase II studies on this schedule is 400 mg m–2cycle–1. © 2000 Cancer Research Campaig

    Mapping species distributions: A comparison of skilled naturalist and lay citizen science recording

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    To assess the ability of traditional biological recording schemes and lay citizen science approaches to gather data on species distributions and changes therein, we examined bumblebee records from the UK’s national repository (National Biodiversity Network) and from BeeWatch. The two recording approaches revealed similar relative abundances of bumblebee species but different geographical distributions. For the widespread common carder (Bombus pascuorum), traditional recording scheme data were patchy, both spatially and temporally, reflecting active record centre rather than species distribution. Lay citizen science records displayed more extensive geographic coverage, reflecting human population density, thus offering better opportunities to account for recording effort. For the rapidly spreading tree bumblebee (Bombus hypnorum), both recording approaches revealed similar distributions due to a dedicated mapping project which overcame the patchy nature of naturalist records. We recommend, where possible, complementing skilled naturalist recording with lay citizen science programmes to obtain a nation-wide capability, and stress the need for timely uploading of data to the national repository

    Updating known distribution models for forecasting climate change impact on endangered species

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    To plan endangered species conservation and to design adequate management programmes, it is necessary to predict their distributional response to climate change, especially under the current situation of rapid change. However, these predictions are customarily done by relating de novo the distribution of the species with climatic conditions with no regard of previously available knowledge about the factors affecting the species distribution. We propose to take advantage of known species distribution models, but proceeding to update them with the variables yielded by climatic models before projecting them to the future. To exemplify our proposal, the availability of suitable habitat across Spain for the endangered Bonelli’s Eagle (Aquila fasciata) was modelled by updating a pre-existing model based on current climate and topography to a combination of different general circulation models and Special Report on Emissions Scenarios. Our results suggested that the main threat for this endangered species would not be climate change, since all forecasting models show that its distribution will be maintained and increased in mainland Spain for all the XXI century. We remark on the importance of linking conservation biology with distribution modelling by updating existing models, frequently available for endangered species, considering all the known factors conditioning the species’ distribution, instead of building new models that are based on climate change variables only.Ministerio de Ciencia e Innovación and FEDER (project CGL2009-11316/BOS

    Long‐Distance Natal Dispersal Is Relatively Frequent and Correlated with Environmental Factors in a Widespread Raptor

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    Dispersal is a critical process influencing population dynamics and responses to global change. Long‐distance dispersal (LDD) can be especially important for gene flow and adaptability, although little is known about the factors influencing LDD because studying large‐scale movements is challenging and LDD tends to be observed less frequently than shorter‐distance dispersal (SDD). We sought to understand patterns of natal dispersal at a large scale, specifically aiming to understand the relative frequency of LDD compared to SDD and correlates of dispersal distances. We used bird banding and encounter data for American kestrels (Falco sparverius) to investigate the effects of sex, migration strategy, population density, weather, year and agricultural land cover on LDD frequency, LDD distance and SDD distance in North America from 1961 to 2015. Nearly half of all natal dispersal (48.9%) was LDD (classified as \u3e30 km), and the likelihood of LDD was positively associated with the proportion of agricultural land cover around natal sites. Correlates of distance differed between LDD and SDD movements. LDD distance was positively correlated with latitude, a proxy for migration strategy, suggesting that migratory individuals disperse farther than residents. Distance of LDD in males was positively associated with maximum summer temperature. We did not find sex‐bias or an effect of population density in LDD distance or frequency. Within SDD, females tended to disperse farther than males, and distance was positively correlated with density. Sampling affected all responses, likely because local studies more frequently capture SDD within study areas. Our findings that LDD occurs at a relatively high frequency and is related to different proximate factors from SDD, including a lack of sex‐bias in LDD, suggest that LDD may be more common than previously reported, and LDD and SDD may be distinct processes rather than two outcomes originating from a single dispersal distribution. To our knowledge, this is the first evidence that LDD and SDD may be separate processes in an avian species, and suggests that environmental change may have different outcomes on the two processes

    The need for large-scale distribution data to estimate regional changes in species richness under future climate change

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    Aim: Species distribution models built with geographically restricted data often fail to capture the full range of conditions experienced by species across their entire distribution area. Using such models to predict distribution shifts under future environmental change may, therefore, produce biased projections. However, restricted-scale models have the potential to include a larger sample of taxa for which distribution data are available and to provide finer-resolution projections that are better applied to conservation planning than the forecasts of broad-scale models. We examine the circumstances under which the projected shifts in species richness patterns derived from restricted-scale and broad-scale models are most likely to be similar. Location: Europe. Methods: The distribution of butterflies in Finland, Belgium/Netherlands and Spain was modelled based on restricted-scale (local) and broad-scale (continental) distribution and climate data. Both types of models were projected under future climate change scenarios to assess potential changes in species richness. Results: In Finland, species richness was projected to increase strongly based on restricted-scale models and to decrease slightly with broad-scale models. In Belgium/Netherlands, restricted-scale models projected a larger decrease in richness than broad-scale models. In Spain, both models projected a slight decrease in richness. We obtained similar projections based on restricted-scale and broad-scale models only in Spain because the climatic conditions available here covered the warm part of the distributions of butterflies better than in Finland and Belgium/Netherlands. Main conclusions: Restricted-scale models that fail to capture the warm part of species distributions produce biased estimates of future changes in species richness when projected under climatic conditions with no modern analogue in the study area. We recommend the use of distribution data beyond the boundaries of the study area to capture the part of the species response curves reflecting the climatic conditions that will prevail within that area in the future.Peer reviewe

    Chapter 4. In search of relevant predictors for marine species distribution modelling using the MarineSPEED benchmark dataset

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    Aim: Ideally, datasets for species distribution modelling (SDM) contain evenly sampled records covering the entire distribution of the species, confirmed absences and auxiliary ecophysiological data allowing informed decisions on relevant predictors. Unfortunately, these criteria are rarely met for marine organisms for which distributions are too often only scantly characterized and absences generally not recorded. Here, we investigate predictor relevance as a function of modelling algorithms and settings for a global dataset of marine species.Location: Global marine.Methods: We selected well-studied and identifiable species from all major marine taxonomic groups. Distribution records were compiled from public sources (e.g., OBIS, GBIF, Reef Life Survey) and linked to environmental data from Bio-ORACLE and MARSPEC. Using this dataset, predictor relevance was analysed under different variations of modelling algorithms, numbers of predictor variables, cross-validation strategies, sampling bias mitigation methods, evaluation methods and ranking methods. SDMs for all combinations of predictors from eight correlation groups were fitted and ranked, from which the top five predictors were selected as the most relevant. Results: We collected two million distribution records from 514 species across 18 phyla. Mean sea surface temperature and calcite are, respectively, the most relevant and irrelevant predictors. A less clear pattern was derived from the other predictors. The biggest differences in predictor relevance were induced by varying the number of predictors, the modelling algorithm and the sample selection bias correction. The distribution data and associated environmental data are made available through the R package marinespeed and at http://marinespeed.org.Main conclusions: While temperature is a relevant predictor of global marine species distributions, considerable variation in predictor relevance is linked to the SDM set-up. We promote the usage of a standardized benchmark dataset (MarineSPEED) for methodological SDM studies

    Relating Habitat and Climatic Niches in Birds

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    Predicting species' responses to the combined effects of habitat and climate changes has become a major challenge in ecology and conservation biology. However, the effects of climatic and habitat gradients on species distributions have generally been considered separately. Here, we explore the relationships between the habitat and thermal dimensions of the ecological niche in European common birds. Using data from the French Breeding Bird Survey, a large-scale bird monitoring program, we correlated the habitat and thermal positions and breadths of 74 bird species, controlling for life history traits and phylogeny. We found that cold climate species tend to have niche positions in closed habitats, as expected by the conjunction of the biogeographic history of birds' habitats, and their current continent-scale gradients. We also report a positive correlation between thermal and habitat niche breadths, a pattern consistent with macroecological predictions concerning the processes shaping species' distributions. Our results suggest that the relationships between the climatic and habitat components of the niche have to be taken into account to understand and predict changes in species' distributions
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