Genome sequence of a novel alloherpesvirus isolated from glass catfish (Kryptopterus bicirrhis)

The 149,343-bp genome of silurid herpesvirus 1, which was isolated in Thailand from glass catfish, was sequenced. The genome was most closely related to that of ictalurid herpesvirus 2, which infects black bullhead catfish. To our knowledge, this was the first silurid catfish alloherpesvirus genome to be sequenced

Expected correlates and outcomes of childhood gender nonconformity

Participants were presented with one of ten vignettes describing a male or female child character who varied in gender-related interests and behaviors from strongly masculine to strongly feminine. Participants thought masculine and feminine children would be masculine and feminine in adulthood, respectively, and that masculinity would be related to externalizing and femininity to internalizing. They thought that gender-nonconforming children would experience more pressure to change their behavior, and that they would be less likely to be exclusively heterosexual in adulthood

Performance Characteristics of Fecal Immunochemical Tests for Colorectal Cancer and Advanced Adenomatous Polyps: A Systematic Review and Meta-analysis

Background: Studies report inconsistent performance of fecal immunochemical tests (FITs) for colorectal cancer (CRC) and advanced adenomas. Purpose: To summarize performance characteristics of FITs for CRC and advanced adenomas in average-risk persons undergoing screening colonoscopy (reference standard) and to identify factors affecting these characteristics. Data Sources: Ovid MEDLINE, PubMed, Embase, and the Cochrane Library from inception through October 2018; reference lists of studies and reviews. Study Selection: Two reviewers independently screened records to identify published English-language prospective or retrospective observational studies that evaluated FIT sensitivity and specificity for colonoscopic findings in asymptomatic, average-risk adults. Data Extraction: Two authors independently extracted data and evaluated study quality. Data Synthesis: Thirty-one studies (120 255 participants; 18 FITs) were included; all were judged to have low to moderate risk of bias. Performance characteristics depended on the threshold for a positive result. A threshold of 10 µg/g resulted in sensitivity of 0.91 (95% CI, 0.84 to 0.95) and a negative likelihood ratio of 0.10 (CI, 0.06 to 0.19) for CRC, whereas a threshold of greater than 20 µg/g resulted in specificity of 0.95 (CI, 0.94 to 0.96) and a positive likelihood ratio of 15.49 (CI, 9.82 to 22.39). For advanced adenomas, sensitivity was 0.40 (CI, 0.33 to 0.47) and the negative likelihood ratio was 0.67 (CI, 0.57 to 0.78) at 10 µg/g, and specificity was 0.95 (CI, 0.94 to 0.96) and the positive likelihood ratio was 5.86 (CI, 3.77 to 8.97) at greater than 20 µg/g. Studies had low to high heterogeneity, depending on the threshold. Although several FITs had adequate performance, sensitivity and specificity for CRC for 1 qualitative FIT were 0.90 and 0.91, respectively, at its single threshold of 10 µg/g; positive and negative likelihood ratios were 10.13 and 0.11, respectively. Comparison of 3 FITs at 3 thresholds was inconclusive: CIs overlapped, and the comparisons were across rather than within studies. Limitations: Only English-language studies were included. Incomplete reporting limited quality assessment of some evidence. Performance characteristics are for 1-time rather than serial testing. Conclusion: Single-application FITs have moderate to high sensitivity and specificity for CRC, depending on the positivity threshold. Sensitivity of 1-time testing for advanced adenomas is low, regardless of the threshold

Enhancing genome assemblies by integrating non-sequence based data

INTRODUCTION Many genome projects were underway before the advent of high-throughput sequencing and have thus been supported by a wealth of genome information from other technologies. Such information frequently takes the form of linkage and physical maps, both of which can provide a substantial amount of data useful in de novo sequencing projects. Furthermore, the recent abundance of genome resources enables the use of conserved synteny maps identified in related species to further enhance genome assemblies. METHODS The tammar wallaby (Macropus eugenii) is a model marsupial mammal with a low coverage genome. However, we have access to extensive comparative maps containing over 14,000 markers constructed through the physical mapping of conserved loci, chromosome painting and comprehensive linkage maps. Using a custom Bioperl pipeline, information from the maps was aligned to assembled tammar wallaby contigs using BLAT. This data was used to construct pseudo paired-end libraries with intervals ranging from 5-10 MB. We then used Bambus (a program designed to scaffold eukaryotic genomes by ordering and orienting contigs through the use of paired-end data) to scaffold our libraries. To determine how map data compares to sequence based approaches to enhance assemblies, we repeated the experiment using a 0.5× coverage of unique reads from 4 KB and 8 KB Illumina paired-end libraries. Finally, we combined both the sequence and non-sequence-based data to determine how a combined approach could further enhance the quality of the low coverage de novo reconstruction of the tammar wallaby genome. RESULTS Using the map data alone, we were able order 2.2% of the initial contigs into scaffolds, and increase the N50 scaffold size to 39 KB (36 KB in the original assembly). Using only the 0.5× paired-end sequence based data, 53% of the initial contigs were assigned to scaffolds. Combining both data sets resulted in a further 2% increase in the number of initial contigs integrated into a scaffold (55% total) but a 35% increase in N50 scaffold size over the use of sequence-based data alone. CONCLUSIONS We provide a relatively simple pipeline utilizing existing bioinformatics tools to integrate map data into a genome assembly which is available at http://www.mcb.uconn.edu/fac.php?name=paska. While the map data only contributed minimally to assigning the initial contigs to scaffolds in the new assembly, it greatly increased the N50 size. This process added structure to our low coverage assembly, greatly increasing its utility in further analyses

Streambank Erosion in Two Watersheds of the Central Claypan Region of Missouri, United States

This study was undertaken to assess the importance of streambank erosion to the total in-stream sediment of two agricultural watersheds within the Central Claypan Areas. The objective of this research was to determine the effect of stream order, adjacent land use, and season on streambank erosion rates. Thirty-four study sites were established in 2007 and 2008 within Crooked and Otter Creek watersheds, two claypan watersheds located in northeastern Missouri. At each site, field assessments of severely to very severely eroding bank length were determined along 300 to 400 m (984 to 1,312 ft) stream reaches. A factorial experimental design was implemented with four land uses (crop, forest, pasture, and riparian forest), three seasons, and three stream orders (1st, 2nd, and 3rd). Each treatment was replicated three times for each stream order, except for the cropped 3rd order treatment as only one suitable treatment site could be found. Streambank erosion was measured using erosion pins, which were installed in randomly assigned plots that included at least 20% of the eroded bank length within each site. The effect of different seasons was assessed by measuring the length of the exposed pins three times per year (March, July, and November). The bulk density and carbon and nitrogen content of bank material were also determined. Sediment loss rates showed that season and the three-way interaction between season, land use, and stream order were highly significant. Erosion rates were consistently higher in the winter months than spring/ summer and fall seasons; however, the significant three-way interaction precluded a simple interpretation of the seasonal effect. Soil nutrient concentration data showed that forest sites had significantly lower C and N concentrations than other land uses. At the watershed scale, bank sediment accounted for 79% to 96% of the total in-stream sediment and 21% to 24% of the total N exported from the study area. These results indicate that streambanks are the dominant source of sediment and a significant source of N in these streams. Therefore, improved management of riparian areas to decrease streambank erosion would result in significant water quality improvement in streams of the Central Claypan Areas in northeastern Missouri

Altered mitochondrial function in fibroblast cell lines derived from disease carriers of spinal muscular atrophy

BackgroundSpinal muscular atrophy (SMA) is an autosomal recessive childhood-onset neuromuscular disease with a carrier frequency of ~1:50. Mitochondrial abnormalities are widespread in patients with SMA. Disease carriers for SMA (i.e., the parents of patients with SMA) are viewed as asymptomatic for SMA disease. As far as we are aware, mitochondria have not been previously examined in SMA carriers, yet as they are maternally inherited, mitochondrial function in SMA carriers has putative implications for disease pathogenesis.MethodsFibroblast cell lines derived from SMA carriers and controls were obtained from two different sources and cultured under standard conditions. The mitochondrial membrane potential, reactive oxygen species (ROS) production, citrate synthase activity, and bioenergetic analysis were examined as measures of mitochondrial function. The mitochondrial genome was also sequenced in a subset of the fibroblast cell lines to identify any mitochondrial DNA variants.ResultsHere, we show a depolarized mitochondrial membrane potential, increased levels of reactive oxygen species, and reduced citrate synthase activity in SMA carriers compared with controls. A likely pathogenic variant in the MT-CO3 gene (which encodes subunit III of cytochrome c oxidase) was also identified in a paternal carrier.ConclusionsThis study was conducted as a preliminary investigation of mitochondrial function in SMA carriers. Our findings suggest that disease carriers of SMA show differences in mitochondrial function, indicative of a subclinical mitochondrial phenotype. Further investigation in a larger sample set is warranted

Targeted Mutagenesis of a Therapeutic Human Monoclonal IgG1 Antibody Prevents Gelation at High Concentrations

A common challenge encountered during development of high concentration monoclonal antibody formulations is preventing self-association. Depending on the antibody and its formulation, self-association can be seen as aggregation, precipitation, opalescence or phase separation. Here we report on an unusual manifestation of self-association, formation of a semi-solid gel or “gelation”. Therapeutic monoclonal antibody C4 was isolated from human B cells based on its strong potency in neutralizing bacterial toxin in animal models. The purified antibody possessed the unusual property of forming a firm, opaque white gel when it was formulated at concentrations \u3e40 mg/mL and the temperature wa

KELT-7b: A hot Jupiter transiting a bright V=8.54 rapidly rotating F-star

We report the discovery of KELT-7b, a transiting hot Jupiter with a mass of $1.28 \pm 0.18$ MJ, radius of $1.53_{-0.047}^{+0.046}$ RJ, and an orbital period of $2.7347749 \pm 0.0000039$ days. The bright host star (HD33643; KELT-7) is an F-star with $V=8.54$, Teff $=6789_{-49}^{+50}$ K, [Fe/H] $=0.139_{-0.081}^{+0.075}$, and $\log{g}=4.149 \pm 0.019$. It has a mass of $1.535_{-0.054}^{+0.066}$ Msun, a radius of $1.732_{-0.045}^{+0.043}$ Rsun, and is the fifth most massive, fifth hottest, and the ninth brightest star known to host a transiting planet. It is also the brightest star around which KELT has discovered a transiting planet. Thus, KELT-7b is an ideal target for detailed characterization given its relatively low surface gravity, high equilibrium temperature, and bright host star. The rapid rotation of the star ($73 \pm 0.5$ km/s) results in a Rossiter-McLaughlin effect with an unusually large amplitude of several hundred m/s. We find that the orbit normal of the planet is likely to be well-aligned with the stellar spin axis, with a projected spin-orbit alignment of $\lambda=9.7 \pm 5.2$ degrees. This is currently the second most rapidly rotating star to have a reflex signal (and thus mass determination) due to a planetary companion measured.Comment: Accepted to The Astronomical Journa

Crystal structures of Burkholderia cenocepacia dihydropteroate synthase in the apo-form and complexed with the product 7,8-dihydropteroate

<p>Abstract</p> <p>Background</p> <p>The enzyme dihydropteroate synthase (DHPS) participates in the <it>de novo </it>synthesis of folate cofactors by catalyzing the formation of 7,8-dihydropteroate from condensation of <it>p</it>-aminobenzoic acid with 6-hydroxymethyl-7,8-dihydropteroate pyrophosphate. DHPS is absent from humans, who acquire folates from diet, and has been validated as an antimicrobial therapeutic target by chemical and genetic means. The bacterium <it>Burkholderia cenocepacia </it>is an opportunistic pathogen and an infective agent of cystic fibrosis patients. The organism is highly resistant to antibiotics and there is a recognized need for the identification of new drugs against <it>Burkholderia </it>and related Gram-negative pathogens. Our characterization of the DHPS active site and interactions with the enzyme product are designed to underpin early stage drug discovery.</p> <p>Results</p> <p>An efficient recombinant protein expression system for DHPS from <it>B. cenocepacia </it>(<it>Bc</it>DHPS) was prepared, the dimeric enzyme purified in high yield and crystallized. The structure of the apo-enzyme and the complex with the product 7,8-dihydropteroate have been determined to 2.35 Å and 1.95 Å resolution respectively in distinct orthorhombic crystal forms. The latter represents the first crystal structure of the DHPS-pterin product complex, reveals key interactions involved in ligand binding, and reinforces data generated by other structural studies. Comparisons with orthologues identify plasticity near the substrate-binding pocket and in particular a range of loop conformations that contribute to the architecture of the DHPS active site. These structural data provide a foundation for hit discovery. An intriguing observation, an artifact of the analysis, that of a potential sulfenamide bond within the ligand complex structure is mentioned.</p> <p>Conclusion</p> <p>Structural similarities between <it>Bc</it>DHPS and orthologues from other Gram-negative species are evident as expected on the basis of a high level of sequence identity. The presence of 7,8-dihydropteroate in the binding site provides details about ligand recognition by the enzyme and the different states of the enzyme allow us to visualize distinct conformational states of loops adjacent to the active site. Improved drugs to combat infections by <it>Burkholderia sp. </it>and related Gram-negative bacteria are sought and our study now provides templates to assist that process and allow us to discuss new ways of inhibiting DHPS.</p