Local adaptation of a bacterium is as important as its presence in structuring a natural microbial community

This is the final version of the article. Available from Springer Nature via the DOI in this record.Local adaptation of a species can affect community composition, yet the importance of local adaptation compared with species presence per se is unknown. Here we determine how a compost bacterial community exposed to elevated temperature changes over 2 months as a result of the presence of a focal bacterium, Pseudomonas fluorescens SBW25, that had been pre-adapted or not to the compost for 48 days. The effect of local adaptation on community composition is as great as the effect of species presence per se, with these results robust to the presence of an additional strong selection pressure: an SBW25-specific virus. These findings suggest that evolution occurring over ecological time scales can be a key driver of the structure of natural microbial communities, particularly in situations where some species have an evolutionary head start following large perturbations, such as exposure to antibiotics or crop planting and harvesting.The work was funded by BBSRC, AXA Research fund and NERC. P.G. was supported by a Marie Curie Intra-European Fellowship within the European Commission 7th Framework Program (PIEF-GA-2010-272945), and acknowledges the Spanish MINECO support (AGL2014-59556-R). A.B. was supported by the Royal Society (UK). L.D.M. acknowledges the KU Leuven Research Fund support PF/2010/07

New primary renal diagnosis codes for the ERA-EDTA

The European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) Registry has produced a new set of primary renal diagnosis (PRD) codes that are intended for use by affiliated registries. It is designed specifically for use in renal centres and registries but is aligned with international coding standards supported by the WHO (International Classification of Diseases) and the International Health Terminology Standards Development Organization (SNOMED Clinical Terms). It is available as supplementary material to this paper and free on the internet for non-commercial, clinical, quality improvement and research use, and by agreement with the ERA-EDTA Registry for use by commercial organizations. Conversion between the old and the new PRD codes is possible. The new codes are very flexible and will be actively managed to keep them up-to-date and to ensure that renal medicine can remain at the forefront of the electronic revolution in medicine, epidemiology research and the use of decision support systems to improve the care of patients

Strong differences in the clonal variation of two Daphnia species from mountain lakes affected by overwintering strategy

<p>Abstract</p> <p>Background</p> <p>The population structure of cyclical parthenogens such as water fleas is strongly influenced by the frequency of alternations between sexual and asexual (parthenogenetic) reproduction, which may differ among populations and species. We studied genetic variation within six populations of two closely related species of water fleas of the genus <it>Daphnia </it>(Crustacea, Cladocera). <it>D. galeata </it>and <it>D. longispina </it>both occur in lakes in the Tatra Mountains (Central Europe), but their populations show distinct life history strategies in that region. In three studied lakes inhabited by <it>D. galeata</it>, daphnids overwinter under the ice as adult females. In contrast, in lakes inhabited by <it>D. longispina</it>, populations apparently disappear from the water column and overwinter as dormant eggs in lake sediments. We investigated to what extent these different strategies lead to differences in the clonal composition of late summer populations.</p> <p>Results</p> <p>Analysis of genetic variation at nine microsatellite loci revealed that clonal richness (expressed as the proportion of different multilocus genotypes, MLGs, in the whole analysed sample) consistently differed between the two studied species. In the three <it>D. longispina </it>populations, very high clonal richness was found (MLG/N ranging from 0.97 to 1.00), whereas in <it>D. galeata </it>it was much lower (0.05 to 0.50). The dominant MLGs in all <it>D. galeata </it>populations were heterozygous at five or more loci, suggesting that such individuals all represented the same clonal lineages rather than insufficiently resolved groups of different clones.</p> <p>Conclusions</p> <p>The low clonal diversities and significant deviations from Hardy-Weinberg equilibrium in <it>D. galeata </it>populations were likely a consequence of strong clonal erosion over extended periods of time (several years or even decades) and the limited influence of sexual reproduction. Our data reveal that populations of closely related <it>Daphnia </it>species living in relatively similar habitats (permanent, oligotrophic mountain lakes) within the same region may show strikingly different genetic structures, which most likely depend on their reproductive strategy during unfavourable periods. We assume that similar impacts of life history on population structures are also relevant for other cyclical parthenogen groups. In extreme cases, prolonged clonal erosion may result in the dominance of a single clone within a population, which might limit its microevolutionary potential if selection pressures suddenly change.</p

On the estimation of normal copula discrete regression models using the continuous extension and simulated likelihood

The continuous extension of a discrete random variable is amongst the computational methods used for estimation of multivariate normal copula-based models with discrete margins. Its advantage is that the likelihood can be derived conveniently under the theory for copula models with continuous margins, but there has not been a clear analysis of the adequacy of this method. We investigate the asymptotic and small-sample efficiency of two variants of the method for estimating the multivariate normal copula with univariate binary, Poisson, and negative binomial regressions, and show that they lead to biased estimates for the latent correlations, and the univariate marginal parameters that are not regression coefficients. We implement a maximum simulated likelihood method, which is based on evaluating the multidimensional integrals of the likelihood with randomized quasi Monte Carlo methods. Asymptotic and small-sample efficiency calculations show that our method is nearly as efficient as maximum likelihood for fully specified multivariate normal copula-based models. An illustrative example is given to show the use of our simulated likelihood method

Polymorphisms in the ficolin 1 gene (FCN1) are associated with susceptibility to the development of rheumatoid arthritis

Objectives. We investigated the possible association of rheumatoid arthritis (RA) with single nucleotide polymorphisms (SNP) within the ficolin (FCN) genes. Two SNPs in the FCN1 gene, four SNPs in the FCN2 gene and one SNP in the FCN3 gene were studied. Methods. The SNPs within the FCN genes were detected by an experimental INNO-LiPA methodology (Innogenetics, Belgium) in a population consisting of 338 RA patients and 595 controls. The significant SNPs were further evaluated in two subpopulations and related to carriage of the human leukocyte antigen-shared epitope (HLA-SE), rheumatoid factor (RF) and the presence of anti-citrullinated protein/peptide antibodies (ACPA). Results. Two SNPs in the FCN1 gene were significantly associated with RA: the A allele rs2989727 was significantly increased in RA patients (67%) compared with controls (60%) (P = 0.002). Also, the frequency of the G allele of rs1071583 was increased in RA patients (68%) compared with controls (61%) (P = 0.003). Analysis of agreement between SNPs suggested strong linkage between rs2989727 and rs1071583. Carriage of a FCN1 SNP was independent of carriage of the HLA-SE, RF status and ACPA positivity. Conclusions. We describe two linked SNPs in the FCN1 gene that are associated with the development of RA

Lack of phylogeographic structure in the freshwater cyanobacterium <i>Microcystis aeruginosa</i> suggests global dispersal

Background: Free-living microorganisms have long been assumed to have ubiquitous distributions with little biogeographic signature because they typically exhibit high dispersal potential and large population sizes. However, molecular data provide contrasting results and it is far from clear to what extent dispersal limitation determines geographicstructuring of microbial populations. We aimed to determine biogeographical patterns of the bloom-forming freshwatercyanobacterium Microcystis aeruginosa. Being widely distributed on a global scale but patchily on a regional scale, this prokaryote is an ideal model organism to study microbial dispersal and biogeography.Methodology/Principal Findings: The phylogeography of M. aeruginosa was studied based on a dataset of 311 rDNAinternal transcribed spacer (ITS) sequences sampled from six continents. Richness of ITS sequences was high (239 ITS typeswere detected). Genetic divergence among ITS types averaged 4% (maximum pairwise divergence was 13%). Preliminary analyses revealed nearly completely unresolved phylogenetic relationships and a lack of genetic structure among all sequences due to extensive homoplasy at multiple hypervariable sites. After correcting for this, still no clear phylogeographic structure was detected, and no pattern of isolation by distance was found on a global scale. Concomitantly, genetic differentiation among continents was marginal, whereas variation within continents was high and was mostly shared with all other continents. Similarly, no genetic structure across climate zones was detected.Conclusions/Significance: The high overall diversity and wide global distribution of common ITS types in combination with the lack of phylogeographic structure suggest that intercontinental dispersal of M. aeruginosa ITS types is not rare, and that this species might have a truly cosmopolitan distribution

Imaging of atherosclerosis, targeting LFA-1 on inflammatory cells with 111In-DANBIRT

Background: 111In-DOTA-butylamino-NorBIRT (DANBIRT) is a novel radioligand which binds to Leukocyte Function-associated Antigen-1 (LFA-1), expressed on inflammatory cells. This study evaluated 111In-DANBIRT for the visualization of atherosclerotic plaque inflammation in mice. Methods and Results: ApoE−/− mice, fed an atherogenic diet up to 20 weeks (n = 10), were imaged by SPECT/CT 3 hours post injection of 111In-DANBIRT (~ 200 pmol, ~ 40 MBq). Focal spots of 111In-DANBIRT were visible in the aortic arch of all animals, with an average Target-to-Background Ratio (TBR) of 1.7 ± 0.5. In vivo imaging results were validated by ex vivo SPECT/CT imaging, with a TBR up to 11.5 (range 2.6 to 11.5). Plaques, identified by Oil Red O lipid-staining on excised arteries, co-localized with 111In-DANBIRT uptake as determined by ex vivo autoradiography. Subsequent histological processing and in vitro autoradiography confirmed 111In-DANBIRT uptake at plaque areas containing CD68 expressing macrophages and LFA-1 expressing inflammatory cells. Ex vivo incubation of a human carotid endarterectomy specimen with 111In-DANBIRT (~ 950 nmol, ~ 190 MBq) for 2 hours showed heterogeneous plaque uptake on SPECT/CT, after which immunohistochemical analysis demonstrated co-localization of 111In-DANBIRT uptake and CD68 and LFA-1 expressing cells. Conclusions: Our results indicate the potential of radiolabeled DANBIRT as a relevant imaging radioligand for non-invasive evaluation of atherosclerotic inflammation

Imaging inflammation in atherosclerotic plaques, targeting SST2 with [111In]In-DOTA-JR11

Background: Imaging Somatostatin Subtype Receptor 2 (SST2) expressing macrophages by [DOTA,Tyr3]-octreotate (DOTATATE) has proven successful for plaque detection. DOTA-JR11 is a SST2 targeting ligand with a five times higher tumor uptake than DOTATATE, and holds promise to improve plaque imaging. The aim of this study was to evaluate the potential of DOTA-JR11 for plaque detection. Methods and Results: Atherosclerotic ApoE−/− mice (n = 22) fed an atherogenic diet were imaged by SPECT/CT two hours post injection of [111In]In-DOTA-JR11 (~ 200 pmol, ~ 50 MBq). In vivo plaque uptake of [111In]In-DOTA-JR11 was visible in all mice, with a target-to-background-ratio (TBR) of 2.23 ± 0.35. Post-mortem scans after thymectomy and ex vivo scans of the arteries after excision of the arteries confirmed plaque uptake of the radioligand with TBRs of 2.46 ± 0.52 and 3.43 ± 1.45 respectively. Oil red O lipid-staining and ex vivo autoradiography of excised arteries showed [111In]In-DOTA-JR11 uptake at plaque locations. Histological processing showed CD68 (macrophages) and SST2 expressing cells in plaques. SPECT/CT, in vitro autoradiography and immunohistochemistry performed on slices of a human carotid endarterectomy sample showed [111In]In-DOTA-JR11 uptake at plaque locations containing CD68 and SST2 expressing cells. Conclusions: The results of this study indicate DOTA-JR1