Source tracking swine fecal waste in surface water proximal to swine concentrated animal feeding operations

Swine farming has gone through many changes in the last few decades, resulting in operations with a high animal density known as confined animal feeding operations (CAFOs). These operations produce a large quantity of fecal waste whose environmental impacts are not well understood. The purpose of this study was to investigate microbial water quality in surface waters proximal to swine CAFOs including microbial source tracking of fecal microbes specific to swine. For one year, surface water samples at up- and downstream sites proximal to swine CAFO lagoon waste land application sites were tested for fecal indicator bacteria (fecal coliforms, Escherichia coli and Enterococcus) and candidate swine-specific microbial source-tracking (MST) markers (Bacteroidales Pig-1-Bac, Pig-2-Bac, and Pig-Bac-2, and methanogen P23-2). Testing of 187 samples showed high fecal indicator bacteria concentrations at both up- and downstream sites. Overall, 40%, 23%, and 61% of samples exceeded state and federal recreational water quality guidelines for fecal coliforms, E. coli, and Enterococcus, respectively. Pig-1-Bac and Pig-2-Bac showed the highest specificity to swine fecal wastes and were 2.47 (95% confidence interval [CI] = 1.03, 5.94) and 2.30 times (95% CI = 0.90, 5.88) as prevalent proximal down- than proximal upstream of swine CAFOs, respectively. Pig-1-Bac and Pig-2-Bac were also 2.87 (95% CI = 1.21, 6.80) and 3.36 (95% CI = 1.34, 8.41) times as prevalent when 48 hour antecedent rainfall was greater than versus less than the mean, respectively. Results suggest diffuse and overall poor sanitary quality of surface waters where swine CAFO density is high. Pig-1-Bac and Pig-2-Bac are useful for tracking off-site conveyance of swine fecal wastes into surface waters proximal to and downstream of swine CAFOs and during rain events

Estimating the horizontal and vertical direction-of-arrival of water-borne seismic signals in the northern Philippine Sea

Author Posting. © Acoustical Society of America, 2013. This article is posted here by permission of Acoustical Society of America for personal use, not for redistribution. The definitive version was published in Journal of the Acoustical Society of America 134 (2013): 3282, doi:10.1121/1.4818843.Conventional and adaptive plane-wave beamforming with simultaneous recordings by large-aperture horizontal and vertical line arrays during the 2009 Philippine Sea Engineering Test (PhilSea09) reveal the rate of occurrence and the two-dimensional arrival structure of seismic phases that couple into the deep ocean. A ship-deployed, controlled acoustic source was used to evaluate performance of the horizontal array for a range of beamformer adaptiveness levels. Ninety T-phases from unique azimuths were recorded between Yeardays 107 to 119. T-phase azimuth and S-minus-P-phase time-of-arrival range estimates were validated using United States Geological Survey seismic monitoring network data. Analysis of phases from a seismic event that occurred on Yearday 112 near the east coast of Taiwan approximately 450 km from the arrays revealed a 22° clockwise evolution of T-phase azimuth over 90 s. Two hypotheses to explain such evolution—body wave excitation of multiple sources or in-water scattering—are presented based on T-phase origin sites at the intersection of azimuthal great circle paths and ridge/coastal bathymetry. Propagation timing between the source, scattering region, and array position suggests the mechanism behind the evolution involved scattering of the T-phase from the Ryukyu Ridge and a T-phase formation/scattering location estimation error of approximately 3.2 km.This research is supported by the Office of Naval Research, both the Applied Research Laboratory program and Code 322(OA)

Deep water towed array measurements at close range

Author Posting. © Acoustical Society of America, 2013. This article is posted here by permission of Acoustical Society of America for personal use, not for redistribution. The definitive version was published in Journal of the Acoustical Society of America 134 (2013): 3230, doi:10.1121/1.4818869.During the North Pacific Acoustic Laboratory Philippine Sea 2009 experiment, towed array receptions were made from a towed source as the two ships transited from a separation of several Convergence Zones through a Closest Point of Approach at 3 km. A combination of narrowband tones and broadband pulses were transmitted covering the frequency band 79–535 Hz. The received energy arrives from two general paths—direct path and bottom bounce. Bearing-time records of the narrowband arrivals at times show a 35° spread in the angle of arrival of the bottom bounce energy. Doppler processing of the tones shows significant frequency spread of the bottom bounce energy. Two-dimensional modeling using measured bathymetry, a geoacoustic parameterization based upon the geological record, and measured sound-speed field was performed. Inclusion of the effects of seafloor roughness and surface waves shows that in-plane scattering from rough interfaces can explain much of the observed spread in the arrivals. Evidence of out-of-plane scattering does exist, however, at short ranges. The amount of out-of-plane scattering is best observed in the broadband impulse-beam response analysis, which in-plane surface roughness modeling cannot explain.This work was supported by the Office of Naval Research, Ocean Acoustics, under contract N00014-11-M-0170

Whole genome analysis for 163 gRNAs in Cas9-edited mice reveals minimal off-target activity.

Genome editing with CRISPR-associated (Cas) proteins holds exceptional promise for correcting variants causing genetic disease. To realize this promise, off-target genomic changes cannot occur during the editing process. Here, we use whole genome sequencing to compare the genomes of 50 Cas9-edited founder mice to 28 untreated control mice to assess the occurrence of S. pyogenes Cas9-induced off-target mutagenesis. Computational analysis of whole-genome sequencing data detects 26 unique sequence variants at 23 predicted off-target sites for 18/163 guides used. While computationally detected variants are identified in 30% (15/50) of Cas9 gene-edited founder animals, only 38% (10/26) of the variants in 8/15 founders validate by Sanger sequencing. In vitro assays for Cas9 off-target activity identify only two unpredicted off-target sites present in genome sequencing data. In total, only 4.9% (8/163) of guides tested have detectable off-target activity, a rate of 0.2 Cas9 off-target mutations per founder analyzed. In comparison, we observe ~1,100 unique variants in each mouse regardless of genome exposure to Cas9 indicating off-target variants comprise a small fraction of genetic heterogeneity in Cas9-edited mice. These findings will inform future design and use of Cas9-edited animal models as well as provide context for evaluating off-target potential in genetically diverse patient populations

Comparison of estimated 20-Hz pulse fin whale source levels from the tropical Pacific and Eastern North Atlantic Oceans to other recorded populations

D.H. was funded by the Office of Naval Research (Award: N00014-16-1-2364). J.M.O. was funded under Award: N00014-16-1-2860 also from the Office of Naval Research.Passive acoustic monitoring, mitigation, animal density estimation, and comprehensive understanding of the impact of sound on marine animals all require accurate information on vocalization source level to be most effective. This study focused on examining the uncertainty related to passive sonar equation terms that ultimately contribute to the variability observed in estimated source levels of fin whale calls. Differences in hardware configuration, signal detection methods, sample size, location, and time were considered in interpreting the variability of estimated fin whale source levels. Data from Wake Island in the Pacific Ocean and off Portugal in the Atlantic Ocean provided the opportunity to generate large datasets of estimated source levels to better understand sources of uncertainty leading to the observed variability with and across years. Average seasonal source levels from the Wake Island dataset ranged from 175 to 188 dB re 1 μPa m, while the 2007–2008 seasonal average detected off Portugal was 189 dB re 1 μPa m. Owing to the large inherent variability within and across this and other studies that potentially masks true differences between populations, there is no evidence to conclude that the source level of 20-Hz fin whale calls are regionally or population specific.Publisher PDFPeer reviewe

Entropic Forces Drive Clustering and Spatial Localization of Influenza A M2 During Viral Budding

The influenza A matrix 2 (M2) transmembrane protein facilitates virion release from the infected host cell. In particular, M2 plays a role in the induction of membrane curvature and/or in the scission process whereby the envelope is cut upon virion release. Here we show using coarse-grained computer simulations that various M2 assembly geometries emerge due to an entropic driving force, resulting in compact clusters or linearly extended aggregates as a direct consequence of the lateral membrane stresses. Conditions under which these protein assemblies will cause the lipid membrane to curve are explored and we predict that a critical cluster size is required for this to happen. We go on to demonstrate that under the stress conditions taking place in the cellular membrane as it undergoes large-scale membrane remodeling, the M2 protein will in principle be able to both contribute to curvature induction and sense curvature in order to line up in manifolds where local membrane line tension is high. M2 is found to exhibit linactant behavior in liquid-disordered/liquid-ordered phase-separated lipid mixtures and to be excluded from the liquid-ordered phase, in near-quantitative agreement with experimental observations. Our findings support a role for M2 in membrane remodeling during influenza viral budding both as an inducer and a sensor of membrane curvature, and they suggest a mechanism by which localization of M2 can occur as the virion assembles and releases from the host cell, independent of how the membrane curvature is produced

Multidisciplinary management of acromegaly: A consensus.

The 13th Acromegaly Consensus Conference was held in November 2019 in Fort Lauderdale, Florida, and comprised acromegaly experts including endocrinologists and neurosurgeons who considered optimal approaches for multidisciplinary acromegaly management. Focused discussions reviewed techniques, results, and side effects of surgery, radiotherapy, and medical therapy, and how advances in technology and novel techniques have changed the way these modalities are used alone or in combination. Effects of treatment on patient outcomes were considered, along with strategies for optimizing and personalizing therapeutic approaches. Expert consensus recommendations emphasize how best to implement available treatment options as part of a multidisciplinary approach at Pituitary Tumor Centers of Excellence

Human and mouse essentiality screens as a resource for disease gene discovery.

The identification of causal variants in sequencing studies remains a considerable challenge that can be partially addressed by new gene-specific knowledge. Here, we integrate measures of how essential a gene is to supporting life, as inferred from viability and phenotyping screens performed on knockout mice by the International Mouse Phenotyping Consortium and essentiality screens carried out on human cell lines. We propose a cross-species gene classification across the Full Spectrum of Intolerance to Loss-of-function (FUSIL) and demonstrate that genes in five mutually exclusive FUSIL categories have differing biological properties. Most notably, Mendelian disease genes, particularly those associated with developmental disorders, are highly overrepresented among genes non-essential for cell survival but required for organism development. After screening developmental disorder cases from three independent disease sequencing consortia, we identify potentially pathogenic variants in genes not previously associated with rare diseases. We therefore propose FUSIL as an efficient approach for disease gene discovery

Soft windowing application to improve analysis of high-throughput phenotyping data.

MOTIVATION: High-throughput phenomic projects generate complex data from small treatment and large control groups that increase the power of the analyses but introduce variation over time. A method is needed to utlize a set of temporally local controls that maximizes analytic power while minimizing noise from unspecified environmental factors. RESULTS: Here we introduce \u27soft windowing\u27, a methodological approach that selects a window of time that includes the most appropriate controls for analysis. Using phenotype data from the International Mouse Phenotyping Consortium (IMPC), adaptive windows were applied such that control data collected proximally to mutants were assigned the maximal weight, while data collected earlier or later had less weight. We applied this method to IMPC data and compared the results with those obtained from a standard non-windowed approach. Validation was performed using a resampling approach in which we demonstrate a 10% reduction of false positives from 2.5 million analyses. We applied the method to our production analysis pipeline that establishes genotype-phenotype associations by comparing mutant versus control data. We report an increase of 30% in significant P-values, as well as linkage to 106 versus 99 disease models via phenotype overlap with the soft-windowed and non-windowed approaches, respectively, from a set of 2082 mutant mouse lines. Our method is generalizable and can benefit large-scale human phenomic projects such as the UK Biobank and the All of Us resources. AVAILABILITY AND IMPLEMENTATION: The method is freely available in the R package SmoothWin, available on CRAN http://CRAN.R-project.org/package=SmoothWin. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online