Model Systems of Human Intestinal Flora, to Set Acceptable Daily Intakes of Antimicrobial Residues

The veterinary use of antimicrobial drugs in food producing animals may result in residues in food, that might modify the consumer gut flora. This review compares three model systems that maintain a complex flora of human origin: (i) human flora associated (HFA) continuous flow cultures in chemostats, (ii) HFA mice, and (iii) human volunteers. The "No Microbial Effect Level" of an antibiotic on human flora, measured in one of these models, is used to set the accept¬able daily intake (ADI) for human consumers. Human volunteers trials are most relevant to set microbio¬log¬ical ADI, and may be considered as the "gold standard". However, human trials are very expensive and unethical. HFA chemostats are controlled systems, but tetracycline ADI calculated from a chemostat study is far above result of a human study. HFA mice studies are less expensive and better controlled than human trials. The tetracycline ADI derived from HFA mice studies is close to the ADI directly obtained in human volunteers

Computational analyses of eukaryotic promoters

Computational analysis of eukaryotic promoters is one of the most difficult problems in computational genomics and is essential for understanding gene expression profiles and reverse-engineering gene regulation network circuits. Here I give a basic introduction of the problem and recent update on both experimental and computational approaches. More details may be found in the extended references. This review is based on a summer lecture given at Max Planck Institute at Berlin in 2005

Using Mitochondrial and Nuclear Sequence Data for Disentangling Population Structure in Complex Pest Species: A Case Study with Dermanyssus gallinae

Among global changes induced by human activities, association of breakdown of geographical barriers and impoverishered biodiversity of agroecosystems may have a strong evolutionary impact on pest species. As a consequence of trade networks' expansion, secondary contacts between incipient species, if hybrid incompatibility is not yet reached, may result in hybrid swarms, even more when empty niches are available as usual in crop fields and farms. By providing important sources of genetic novelty for organisms to adapt in changing environments, hybridization may be strongly involved in the emergence of invasive populations

HIV prevention costs and program scale: data from the PANCEA project in five low and middle-income countries

<p>Abstract</p> <p>Background</p> <p>Economic theory and limited empirical data suggest that costs per unit of HIV prevention program output (unit costs) will initially decrease as small programs expand. Unit costs may then reach a nadir and start to increase if expansion continues beyond the economically optimal size. Information on the relationship between scale and unit costs is critical to project the cost of global HIV prevention efforts and to allocate prevention resources efficiently.</p> <p>Methods</p> <p>The "Prevent AIDS: Network for Cost-Effectiveness Analysis" (PANCEA) project collected 2003 and 2004 cost and output data from 206 HIV prevention programs of six types in five countries. The association between scale and efficiency for each intervention type was examined for each country. Our team characterized the direction, shape, and strength of this association by fitting bivariate regression lines to scatter plots of output levels and unit costs. We chose the regression forms with the highest explanatory power (R²).</p> <p>Results</p> <p>Efficiency increased with scale, across all countries and interventions. This association varied within intervention and within country, in terms of the range in scale and efficiency, the best fitting regression form, and the slope of the regression. The fraction of variation in efficiency explained by scale ranged from 26% – 96%. Doubling in scale resulted in reductions in unit costs averaging 34.2% (ranging from 2.4% to 58.0%). Two regression trends, in India, suggested an inflection point beyond which unit costs increased.</p> <p>Conclusion</p> <p>Unit costs decrease with scale across a wide range of service types and volumes. These country and intervention-specific findings can inform projections of the global cost of scaling up HIV prevention efforts.</p

Interference with glycosaminoglycan-chemokine interactions with a probe to alter leukocyte recruitment and inflammation in vivo

In vivo leukocyte recruitment is not fully understood and may result from interactions of chemokines with glycosaminoglycans/GAGs. We previously showed that chlorite-oxidized oxyamylose/COAM binds the neutrophil chemokine GCP-2/CXCL6. Here, mouse chemokine binding by COAM was studied systematically and binding affinities of chemokines to COAM versus GAGs were compared. COAM and heparan sulphate bound the mouse CXC chemokines KC/CXCL1, MIP-2/CXCL2, IP-10/CXCL10 and I-TAC/CXCL11 and the CC chemokine RANTES/CCL5 with affinities in the nanomolar range, whereas no binding interactions were observed for mouse MCP-1/CCL2, MIP-1α/CCL3 and MIP-1β/CCL4. The affinities of COAM-interacting chemokines were similar to or higher than those observed for heparan sulphate. Although COAM did not display chemotactic activity by itself, its co-administration with mouse GCP-2/CXCL6 and MIP-2/CXCL2 or its binding of endogenous chemokines resulted in fast and cooperative peritoneal neutrophil recruitment and in extravasation into the cremaster muscle in vivo. These local GAG mimetic features by COAM within tissues superseded systemic effects and were sufficient and applicable to reduce LPS-induced liver-specific neutrophil recruitment and activation. COAM mimics glycosaminoglycans and is a nontoxic probe for the study of leukocyte recruitment and inflammation in vivo

Co-habiting amphibian species harbor unique skin bacterial communities in wild populations

Although all plant and animal species harbor microbial symbionts, we know surprisingly little about the specificity of microbial communities to their hosts. Few studies have compared the microbiomes of different species of animals, and fewer still have examined animals in the wild. We sampled four pond habitats in Colorado, USA, where multiple amphibian species were present. In total, 32 amphibian individuals were sampled from three different species including northern leopard frogs (Lithobates pipiens), western chorus frogs (Pseudacris triseriata) and tiger salamanders (Ambystoma tigrinum). We compared the diversity and composition of the bacterial communities on the skin of the collected individuals via barcoded pyrosequencing of the 16S rRNA gene. Dominant bacterial phyla included Acidobacteria, Actinobacteria, Bacteriodetes, Cyanobacteria, Firmicutes and Proteobacteria. In total, we found members of 18 bacterial phyla, comparable to the taxonomic diversity typically found on human skin. Levels of bacterial diversity varied strongly across species: L. pipiens had the highest diversity; A. tigrinum the lowest. Host species was a highly significant predictor of bacterial community similarity, and co-habitation within the same pond was not significant, highlighting that the skin-associated bacterial communities do not simply reflect those bacterial communities found in their surrounding environments. Innate species differences thus appear to regulate the structure of skin bacterial communities on amphibians. In light of recent discoveries that some bacteria on amphibian skin have antifungal activity, our finding suggests that host-specific bacteria may have a role in the species-specific resistance to fungal pathogens

Dark energy survey year 1 results: weak lensing shape catalogues

We present two galaxy shape catalogues from the Dark Energy Survey Year 1 data set, covering 1500 deg2 with a median redshift of 0.59. The catalogues cover two main fields: Stripe 82, and an area overlapping the South Pole Telescope survey region. We describe our data analysis process and in particular our shape measurement using two independent shear measurement pipelines, METACALIBRATION and IM3SHAPE. The METACALIBRATION catalogue uses a Gaussian model with an innovative internal calibration scheme, and was applied to riz bands, yielding 34.8M objects. The IM3SHAPE catalogue uses amaximum-likelihood bulge/disc model calibrated using simulations, and was applied to r-band data, yielding 21.9M objects. Both catalogues pass a suite of null tests that demonstrate their fitness for use in weak lensing science. We estimate the 1σ uncertainties in multiplicative shear calibration to be 0.013 and 0.025 for the METACALIBRATION and IM3SHAPE catalogues, respectively

Density split statistics: Cosmological constraints from counts and lensing in cells in des Y1 and SDSS data

© 2018 American Physical Society. We derive cosmological constraints from the probability distribution function (PDF) of evolved large-scale matter density fluctuations. We do this by splitting lines of sight by density based on their count of tracer galaxies, and by measuring both gravitational shear around and counts-in-cells in overdense and underdense lines of sight, in Dark Energy Survey (DES) First Year and Sloan Digital Sky Survey (SDSS) data. Our analysis uses a perturbation theory model [O. Friedrich, Phys. Rev. D 98, 023508 (2018)10.1103/PhysRevD.98.023508] and is validated using N-body simulation realizations and log-normal mocks. It allows us to constrain cosmology, bias and stochasticity of galaxies with respect to matter density and, in addition, the skewness of the matter density field. From a Bayesian model comparison, we find that the data weakly prefer a connection of galaxies and matter that is stochastic beyond Poisson fluctuations on ≤20 arcmin angular smoothing scale. The two stochasticity models we fit yield DES constraints on the matter density Ωm=0.26-0.03+0.04 and Ωm=0.28-0.04+0.05 that are consistent with each other. These values also agree with the DES analysis of galaxy and shear two-point functions (3x2pt, DES Collaboration et al.) that only uses second moments of the PDF. Constraints on σ8 are model dependent (σ8=0.97-0.06+0.07 and 0.80-0.07+0.06 for the two stochasticity models), but consistent with each other and with the 3 x 2pt results if stochasticity is at the low end of the posterior range. As an additional test of gravity, counts and lensing in cells allow to compare the skewness S3 of the matter density PDF to its ΛCDM prediction. We find no evidence of excess skewness in any model or data set, with better than 25 per cent relative precision in the skewness estimate from DES alone

Dark Energy Survey Year 1 results: galaxy-galaxy lensing

We present galaxy-galaxy lensing measurements from 1321 sq. deg. of the Dark Energy Survey (DES) Year 1 (Y1) data. The lens sample consists of a selection of 660,000 red galaxies with high-precision photometric redshifts, known as redMaGiC, split into five tomographic bins in the redshift range 0.15<z<0.9 . We use two different source samples, obtained from the Metacalibration (26 million galaxies) and Im3shape (18 million galaxies) shear estimation codes, which are split into four photometric redshift bins in the range 0.2<z<1.3 . We perform extensive testing of potential systematic effects that can bias the galaxy-galaxy lensing signal, including those from shear estimation, photometric redshifts, and observational properties. Covariances are obtained from jackknife subsamples of the data and validated with a suite of log-normal simulations. We use the shear-ratio geometric test to obtain independent constraints on the mean of the source redshift distributions, providing validation of those obtained from other photo-z studies with the same data. We find consistency between the galaxy bias estimates obtained from our galaxy-galaxy lensing measurements and from galaxy clustering, therefore showing the galaxy-matter cross-correlation coefficient r to be consistent with one, measured over the scales used for the cosmological analysis. The results in this work present one of the three two-point correlation functions, along with galaxy clustering and cosmic shear, used in the DES cosmological analysis of Y1 data, and hence the methodology and the systematics tests presented here provide a critical input for that study as well as for future cosmological analyses in DES and other photometric galaxy surveys