181 research outputs found

    Effects of thermal shocks on the release of radioisotopes and on molten metal target vessels

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    The ISOLDE pulsed proton beam peak power amounts to 500 MW during the 2.4 ms proton pulse. The fraction of the proton pulse energy deposited in the target material is at the origin of severe thermal shocks. Quantitative measurement of their effect on the release of radioelements from ISOLDE targets was obtained by comparison of release profiles measured under different proton beam settings. The thermal shock induced in liquids (Pb, Sn, La) lead to mechanical failure of ISOLDE molten metal target vessels. Failure analysis is presented and discussed in the light of the response of mercury samples submitted to the ISOLDE beam and monitored by high-speed optical systems

    Annotation of two large contiguous regions from the Haemonchus contortus genome using RNA-seq and comparative analysis with Caenorhabditis elegans

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    The genomes of numerous parasitic nematodes are currently being sequenced, but their complexity and size, together with high levels of intra-specific sequence variation and a lack of reference genomes, makes their assembly and annotation a challenging task. Haemonchus contortus is an economically significant parasite of livestock that is widely used for basic research as well as for vaccine development and drug discovery. It is one of many medically and economically important parasites within the strongylid nematode group. This group of parasites has the closest phylogenetic relationship with the model organism Caenorhabditis elegans, making comparative analysis a potentially powerful tool for genome annotation and functional studies. To investigate this hypothesis, we sequenced two contiguous fragments from the H. contortus genome and undertook detailed annotation and comparative analysis with C. elegans. The adult H. contortus transcriptome was sequenced using an Illumina platform and RNA-seq was used to annotate a 409 kb overlapping BAC tiling path relating to the X chromosome and a 181 kb BAC insert relating to chromosome I. In total, 40 genes and 12 putative transposable elements were identified. 97.5% of the annotated genes had detectable homologues in C. elegans of which 60% had putative orthologues, significantly higher than previous analyses based on EST analysis. Gene density appears to be less in H. contortus than in C. elegans, with annotated H. contortus genes being an average of two-to-three times larger than their putative C. elegans orthologues due to a greater intron number and size. Synteny appears high but gene order is generally poorly conserved, although areas of conserved microsynteny are apparent. C. elegans operons appear to be partially conserved in H. contortus. Our findings suggest that a combination of RNA-seq and comparative analysis with C. elegans is a powerful approach for the annotation and analysis of strongylid nematode genomes

    Systematic variation in mRNA 3′-processing signals during mouse spermatogenesis

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    Gene expression and processing during mouse male germ cell maturation (spermatogenesis) is highly specialized. Previous reports have suggested that there is a high incidence of alternative 3′-processing in male germ cell mRNAs, including reduced usage of the canonical polyadenylation signal, AAUAAA. We used EST libraries generated from mouse testicular cells to identify 3′-processing sites used at various stages of spermatogenesis (spermatogonia, spermatocytes and round spermatids) and testicular somatic Sertoli cells. We assessed differences in 3′-processing characteristics in the testicular samples, compared to control sets of widely used 3′-processing sites. Using a new method for comparison of degenerate regulatory elements between sequence samples, we identified significant changes in the use of putative 3′-processing regulatory sequence elements in all spermatogenic cell types. In addition, we observed a trend towards truncated 3′-untranslated regions (3′-UTRs), with the most significant differences apparent in round spermatids. In contrast, Sertoli cells displayed a much smaller trend towards 3′-UTR truncation and no significant difference in 3′-processing regulatory sequences. Finally, we identified a number of genes encoding mRNAs that were specifically subject to alternative 3′-processing during meiosis and postmeiotic development. Our results highlight developmental differences in polyadenylation site choice and in the elements that likely control them during spermatogenesis

    Elucidation of the Bovine Intramammary Bacteriome and Resistome from healthy cows of Swiss dairy farms in the Canton Tessin

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    Healthy, untreated cows of nine dairy herds from the Swiss Canton Tessin were analyzed three times within one year to identify the most abundant species of the intramammary bacteriome. Aseptically collected milk samples were cultured and bacteria identified using MALDI-TOF. Of 256 cows analyzed, 96% were bacteriologically positive and 80% of the 1,024 quarters were positive for at least one bacterial species. 84.5% of the quarters were healthy with somatic cell counts (SCC) < 200,000 cells/mL, whereas 15.5% of the quarters showed a subclinical mastitis (SCC ≥ 200,000 cells/mL). We could assign 1,288 isolates to 104 different bacterial species including 23 predominant species. Non-aureus staphylococci and mammaliicocci (NASM) were most prevalent (14 different species; 73.5% quarters). Staphylococcus xylosus and Mammaliicoccus sciuri accounted for 74.7% of all NASM isolates. To describe the intramammary resistome, 350 isolates of the predominant species were selected and subjected to short-read whole genome sequencing (WGS) and phenotypic antibiotic resistance profiling. While complete genomes of eight type strains were available, the remaining 15 were de novo assembled with long reads as a resource for the community. The 23 complete genomes served for reference-based assembly of the Illumina WGS data. Both chromosomes and mobile genetic elements were examined for antibiotic resistance genes (ARGs) using in-house and online software tools. ARGs were then correlated with phenotypic antibiotic resistance data from minimum inhibitory concentration (MIC). Phenotypic and genomic antimicrobial resistance was isolate-specific. Resistance to clindamycin and oxacillin was most frequently observed (65 and 30%) in Staphylococcus xylosus but could not be linked to chromosomal or plasmid-borne ARGs. However, in several cases, the observed antimicrobial resistance could be explained by the presence of mobile genetic elements like tetK carried on small plasmids. This represents a possible mechanism of transfer between non-pathogenic bacteria and pathogens of the mammary gland within and between herds. The-to our knowledge-most extensive bacteriome reported and the first attempt to link it with the resistome promise to profoundly affect veterinary bacteriology in the future and are highly relevant in a One Health context, in particular for mastitis, the treatment of which still heavily relies on antibiotics

    Genetic Pathway in Acquisition and Loss of Vancomycin Resistance in a Methicillin Resistant Staphylococcus aureus (MRSA) Strain of Clonal Type USA300

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    An isolate of the methicillin-resistant Staphylococcus aureus (MRSA) clone USA300 with reduced susceptibility to vancomycin (SG-R) (i.e, vancomycin-intermediate S. aureus, VISA) and its susceptible “parental” strain (SG-S) were recovered from a patient at the end and at the beginning of an unsuccessful vancomycin therapy. The VISA phenotype was unstable in vitro generating a susceptible revertant strain (SG-rev). The availability of these 3 isogenic strains allowed us to explore genetic correlates of antibiotic resistance as it emerged in vivo. Compared to the susceptible isolate, both the VISA and revertant strains carried the same point mutations in yycH, vraG, yvqF and lspA genes and a substantial deletion within an intergenic region. The revertant strain carried a single additional frameshift mutation in vraS which is part of two component regulatory system VraSR. VISA isolate SG-R showed complex alterations in phenotype: decreased susceptibility to other antibiotics, slow autolysis, abnormal cell division and increased thickness of cell wall. There was also altered expression of 239 genes including down-regulation of major virulence determinants. All phenotypic properties and gene expression profile returned to parental levels in the revertant strain. Introduction of wild type yvqF on a multicopy plasmid into the VISA strain caused loss of resistance along with loss of all the associated phenotypic changes. Introduction of the wild type vraSR into the revertant strain caused recovery of VISA type resistance. The yvqF/vraSR operon seems to function as an on/off switch: mutation in yvqF in strain SG-R turns on the vraSR system, which leads to increase in vancomycin resistance and down-regulation of virulence determinants. Mutation in vraS in the revertant strain turns off this regulatory system accompanied by loss of resistance and normal expression of virulence genes. Down-regulation of virulence genes may provide VISA strains with a “stealth” strategy to evade detection by the host immune system

    The factorial invariance of the CES-D during adolescence: are symptom profiles for depression stable across gender and time?

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    This study examined the factorial invariance of the Center for Epidemiologic Studies of Depression Scale (CES-D) across gender and time during adolescence. The factor structure of the CES-D was compared at four annual measurement waves in a community sample of 2650 Australian adolescents. Confirmatory factor analyses showed that the factor structure of the CES-D was generally invariant across gender and time. However, gender differences were found on three items: for all waves the item 'I had crying spells' was a stronger indicator for depressive affect in females than males. On the final three waves the item 'people were unfriendly' loaded significantly higher on the factor 'Interpersonal Relations' for males than females. On Wave 2 and 3 males interpreted the item 'everything I did was an effort' with a positive connotation, whereas females interpret it with a negative association. These gender-differences are discussed from both a theoretical and a methodological perspective.Marjolein Verhoeven, Michael G. Sawyer and Susan H. Spenc

    The Interaction Between Pubertal Timing and Peer Popularity for Boys and Girls: An Integration of Biological and Interpersonal Perspectives on Adolescent Depression

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    The transition to adolescence marks a time of sharply increased vulnerability to the development of depression, particularly among girls. Past research has examined isolated risk factors from individual theoretical models (e.g., biological, interpersonal, and cognitive) of depression, but few have examined integrative models. This study investigated the conjoint effects of early pubertal timing and popularity in the longitudinal prediction of depressive symptoms. A total of 319 girls and 294 boys (ages 11–14) provided information on their pubertal status, depressive symptoms, and the social status (i.e., popularity) of their peers. Adolescents completed a second measure of depressive symptoms 11 months after the initial time point. Findings supported an integrated biological-interpersonal model in explaining the development of depressive symptoms during adolescence. Early pubertal development was associated with increase in depressive symptoms only when accompanied by low levels of popularity. High levels of popularity buffered the association between early pubertal development and later depressive symptoms. Unexpectedly, these results were significant both for girls and boys. Results are discussed in terms of dynamic systems theories
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