18 research outputs found

    Genomic analysis and relatedness of P2-like phages of the Burkholderia cepacia complex

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    <p>Abstract</p> <p>Background</p> <p>The <it>Burkholderia cepacia </it>complex (BCC) is comprised of at least seventeen Gram-negative species that cause infections in cystic fibrosis patients. Because BCC bacteria are broadly antibiotic resistant, phage therapy is currently being investigated as a possible alternative treatment for these infections. The purpose of our study was to sequence and characterize three novel BCC-specific phages: KS5 (vB_BceM-KS5 or vB_BmuZ-ATCC 17616), KS14 (vB_BceM-KS14) and KL3 (vB_BamM-KL3 or vB_BceZ-CEP511).</p> <p>Results</p> <p>KS5, KS14 and KL3 are myoviruses with the A1 morphotype. The genomes of these phages are between 32317 and 40555 base pairs in length and are predicted to encode between 44 and 52 proteins. These phages have over 50% of their proteins in common with enterobacteria phage P2 and so can be classified as members of the <it>Peduovirinae </it>subfamily and the "P2-like viruses" genus. The BCC phage proteins similar to those encoded by P2 are predominantly structural components involved in virion morphogenesis. As prophages, KS5 and KL3 integrate into an AMP nucleosidase gene and a threonine tRNA gene, respectively. Unlike other P2-like viruses, the KS14 prophage is maintained as a plasmid. The P2 <it>E+E' </it>translational frameshift site is conserved among these three phages and so they are predicted to use frameshifting for expression of two of their tail proteins. The <it>lysBC </it>genes of KS14 and KL3 are similar to those of P2, but in KS5 the organization of these genes suggests that they may have been acquired via horizontal transfer from a phage similar to λ. KS5 contains two sequence elements that are unique among these three phages: an IS<it>Bmu</it>2-like insertion sequence and a reverse transcriptase gene. KL3 encodes an EcoRII-C endonuclease/methylase pair and Vsr endonuclease that are predicted to function during the lytic cycle to cleave non-self DNA, protect the phage genome and repair methylation-induced mutations.</p> <p>Conclusions</p> <p>KS5, KS14 and KL3 are the first BCC-specific phages to be identified as P2-like. As KS14 has previously been shown to be active against <it>Burkholderia cenocepacia in vivo</it>, genomic characterization of these phages is a crucial first step in the development of these and similar phages for clinical use against the BCC.</p

    Designing Military Cockpits to Support a Broad Range of Personnel Body Sizes

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    The Joint Primary Aircraft Training System (JPATS) body size cases provide aircraft designers access to representative Airmen anthropometric dimensions based on a database of air force personnel. To ensure new aircraft can support a broad range of pilot body sizes, designers can reference JPATS case numbers to assure adequate access to specific controls and clearances for ejection. JPATS cases 1 and 7 were added in response to the Air Force’s goal to accommodate 95% of males and females. However, given that someone at the 90th percentile height may not have 90th percentile arm length, a far smaller percentage of accommodation than originally projected is actually achieved. This paper presents a discussion of the limitations of JPATS cases and past evaluation methods, and provides recommendations for methods to utilize during the design process to ensure next generation cockpits can accommodate a broader range of body sizes

    Wartime Sexual Violence, Social Stigmatization and Humanitarian Aid : Survey Evidence from eastern Democratic Republic of Congo

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    Sexual violence by armed groups is common in civil wars. Qualitative studies have shown that victims and their families experience social stigmatization. Stigmatization is viewed as a central mechanism to social exclusion and disintegration impeding post-conflict social, political, and economic recovery. We provide new theory on the social conditions under which rape-related stigma intensifies and decreases. Drawing on an original population-based survey in eastern Democratic Republic of Congo, we find that victims and their families experience higher levels of stigma compared to unaffected families and these effects are dependent on community attitudes and norms. Furthermore, we find that humanitarian support interventions designed to address the social nature of stigma can reduce stigma. Our article significantly expands prior knowledge on a central mechanism in post-conflict recovery by providing a refined theory on wartime rape-related stigma and the role of humanitarian aid in mitigating negative effects based on representative data.publishe

    Phenotypic Landscape of Schizophrenia-Associated Genes Defines Candidates and Their Shared Functions

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    Genomic studies have identified hundreds of candidate genes near loci associated with risk for schizophrenia. To define candidates and their functions, we mutated zebrafish orthologs of 132 human schizophrenia-associated genes. We created a phenotype atlas consisting of whole-brain activity maps, brain structural differences, and profiles of behavioral abnormalities. Phenotypes were diverse but specific, including altered forebrain development and decreased prepulse inhibition. Exploration of these datasets identified promising candidates in more than 10 gene-rich regions, including the magnesium transporter cnnm2 and the translational repressor gigyf2, and revealed shared anatomical sites of activity differences, including the pallium, hypothalamus, and tectum. Single-cell RNA sequencing uncovered an essential role for the understudied transcription factor znf536 in the development of forebrain neurons implicated in social behavior and stress. This phenotypic landscape of schizophrenia-associated genes prioritizes more than 30 candidates for further study and provides hypotheses to bridge the divide between genetic association and biological mechanism
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