112 research outputs found
Genome-level homology and phylogeny of Shewanella (Gammaproteobacteria: lteromonadales: Shewanellaceae)
<p>Abstract</p> <p>Background</p> <p>The explosion in availability of whole genome data provides the opportunity to build phylogenetic hypotheses based on these data as well as the ability to learn more about the genomes themselves. The biological history of genes and genomes can be investigated based on the taxomonic history provided by the phylogeny. A phylogenetic hypothesis based on complete genome data is presented for the genus <it>Shewanella </it>(Gammaproteobacteria: Alteromonadales: Shewanellaceae). Nineteen taxa from <it>Shewanella </it>(16 species and 3 additional strains of one species) as well as three outgroup species representing the genera <it>Aeromonas </it>(Gammaproteobacteria: Aeromonadales: Aeromonadaceae), <it>Alteromonas </it>(Gammaproteobacteria: Alteromonadales: Alteromonadaceae) and <it>Colwellia </it>(Gammaproteobacteria: Alteromonadales: Colwelliaceae) are included for a total of 22 taxa.</p> <p>Results</p> <p>Putatively homologous regions were found across unannotated genomes and tested with a phylogenetic analysis. Two genome-wide data-sets are considered, one including only those genomic regions for which all taxa are represented, which included 3,361,015 aligned nucleotide base-pairs (bp) and a second that additionally includes those regions present in only subsets of taxa, which totaled 12,456,624 aligned bp. Alignment columns in these large data-sets were then randomly sampled to create smaller data-sets. After the phylogenetic hypothesis was generated, genome annotations were projected onto the DNA sequence alignment to compare the historical hypothesis generated by the phylogeny with the functional hypothesis posited by annotation.</p> <p>Conclusions</p> <p>Individual phylogenetic analyses of the 243 locally co-linear genome regions all failed to recover the genome topology, but the smaller data-sets that were random samplings of the large concatenated alignments all produced the genome topology. It is shown that there is not a single orthologous copy of 16S rRNA across the taxon sampling included in this study and that the relationships among the multiple copies are consistent with 16S rRNA undergoing concerted evolution. Unannotated whole genome data can provide excellent raw material for generating hypotheses of historical homology, which can be tested with phylogenetic analysis and compared with hypotheses of gene function.</p
An economic appraisal of the Australian Medical Sheepskin for the prevention of sacral pressure ulcers from a nursing home perspective
<p>Abstract</p> <p>Background</p> <p>Many devices are in use to prevent pressure ulcers, but from most little is known about their effects and costs. One such preventive device is the Australian Medical Sheepskin that has been proven effective in three randomized trials. In this study the costs and savings from the use of the Australian Medical Sheepskin were investigated from the perspective of a nursing home.</p> <p>Methods</p> <p>An economic model was developed in which monetary costs and monetary savings in respect of the sheepskin were balanced against each other. The model was applied to a fictional (Dutch) nursing home with 100 beds for rehabilitation patients and a time horizon of one year. Input variables for the model consisted of investment costs for using the sheepskin (purchase and laundry), and savings through the prevented cases of pressure ulcers. The input values for the investment costs and for the effectiveness were empirically based on a trial with newly admitted rehabilitation patients from eight nursing homes. The input values for the costs of pressure ulcer treatment were estimated by means of four different approaches.</p> <p>Results</p> <p>Investment costs for using the Australian Medical Sheepskin were larger than the monetary savings obtained by preventing pressure ulcers. Use of the Australian Medical Sheepskin involves an additional cost of approximately €2 per patient per day. Preventing one case of a sacral pressure ulcer by means of the Australian Medical Sheepskin involves an investment of €2,974 when the sheepskin is given to all patients. When the sheepskin is selectively used for more critical patients only, the investment to prevent one case of sacral pressure ulcers decreases to €2,479 (pressure ulcer risk patients) or €1,847 (ADL-severely impaired patients). The factors with the strongest influence on the balance are the frequency of changing the sheepskin and the costs of washing related to this. The economic model was hampered by considerable uncertainty in the estimations of the costs of pressure ulcer treatment.</p> <p>Conclusions</p> <p>From a nursing home perspective, the investment costs for use of the Australian Medical Sheepskin in newly admitted rehabilitation patients are larger than the monetary savings obtained by preventing pressure ulcers.</p
Cerebellar gene expression profiles of mouse models for Rett syndrome reveal novel MeCP2 targets
<p>Abstract</p> <p>Background</p> <p>MeCP2, methyl-CpG-binding protein 2, binds to methylated cytosines at CpG dinucleotides, as well as to unmethylated DNA, and affects chromatin condensation. <it>MECP2 </it>mutations in females lead to Rett syndrome, a neurological disorder characterized by developmental stagnation and regression, loss of purposeful hand movements and speech, stereotypic hand movements, deceleration of brain growth, autonomic dysfunction and seizures. Most mutations occur <it>de novo </it>during spermatogenesis. Located at Xq28, <it>MECP2 </it>is subject to X inactivation, and affected females are mosaic. Rare hemizygous males suffer from a severe congenital encephalopathy.</p> <p>Methods</p> <p>To identify the pathways mis-regulated by MeCP2 deficiency, microarray-based global gene expression studies were carried out in cerebellum of <it>Mecp2 </it>mutant mice. We compared transcript levels in mutant/wildtype male sibs of two different MeCP2-deficient mouse models at 2, 4 and 8 weeks of age. Increased transcript levels were evaluated by real-time quantitative RT-PCR. Chromatin immunoprecipitation assays were used to document <it>in vivo </it>MeCP2 binding to promoter regions of candidate target genes.</p> <p>Results</p> <p>Of several hundred genes with altered expression levels in the mutants, twice as many were increased than decreased, and only 27 were differentially expressed at more than one time point. The number of misregulated genes was 30% lower in mice with the exon 3 deletion (<it>Mecp2</it><sup>tm1.1Jae</sup>) than in mice with the larger deletion (<it>Mecp2</it><sup>tm1.1Bird</sup>). Between the mutants, few genes overlapped at each time point. Real-time quantitative RT-PCR assays validated increased transcript levels for four genes: <it>Irak1</it>, interleukin-1 receptor-associated kinase 1; <it>Fxyd1</it>, phospholemman, associated with Na, K-ATPase;<it>Reln</it>, encoding an extracellular signaling molecule essential for neuronal lamination and synaptic plasticity; and <it>Gtl2/Meg3</it>, an imprinted maternally expressed non-translated RNA that serves as a host gene for C/D box snoRNAs and microRNAs. Chromatin immunoprecipitation assays documented <it>in vivo </it>MeCP2 binding to promoter regions of <it>Fxyd1, Reln</it>, and <it>Gtl2</it>.</p> <p>Conclusion</p> <p>Transcriptional profiling of cerebellum failed to detect significant global changes in <it>Mecp2</it>-mutant mice. Increased transcript levels of <it>Irak1, Fxyd1, Reln</it>, and <it>Gtl2 </it>may contribute to the neuronal dysfunction in MeCP2-deficient mice and individuals with Rett syndrome. Our data provide testable hypotheses for future studies of the regulatory or signaling pathways that these genes act on.</p
Comparative analyses imply that the enigmatic sigma factor 54 is a central controller of the bacterial exterior
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95738.pdf (publisher's version ) (Open Access)BACKGROUND: Sigma-54 is a central regulator in many pathogenic bacteria and has been linked to a multitude of cellular processes like nitrogen assimilation and important functional traits such as motility, virulence, and biofilm formation. Until now it has remained obscure whether these phenomena and the control by Sigma-54 share an underlying theme. RESULTS: We have uncovered the commonality by performing a range of comparative genome analyses. A) The presence of Sigma-54 and its associated activators was determined for all sequenced prokaryotes. We observed a phylum-dependent distribution that is suggestive of an evolutionary relationship between Sigma-54 and lipopolysaccharide and flagellar biosynthesis. B) All Sigma-54 activators were identified and annotated. The relation with phosphotransfer-mediated signaling (TCS and PTS) and the transport and assimilation of carboxylates and nitrogen containing metabolites was substantiated. C) The function annotations, that were represented within the genomic context of all genes encoding Sigma-54, its activators and its promoters, were analyzed for intra-phylum representation and inter-phylum conservation. Promoters were localized using a straightforward scoring strategy that was formulated to identify similar motifs. We found clear highly-represented and conserved genetic associations with genes that concern the transport and biosynthesis of the metabolic intermediates of exopolysaccharides, flagella, lipids, lipopolysaccharides, lipoproteins and peptidoglycan. CONCLUSION: Our analyses directly implicate Sigma-54 as a central player in the control over the processes that involve the physical interaction of an organism with its environment like in the colonization of a host (virulence) or the formation of biofilm
Identification of a new lesch-nyhan syndrome mutation (HPRT BRASIL) and analysis of potentially heterozygous females
Therapeutic drug monitoring of benznidazole and nifurtimox: a systematic review and quality assessment of published clinical practice guidelines
Is PEEK cage better than titanium cage in anterior cervical discectomy and fusion surgery? A meta-analysis
Agreement among type 2 diabetes linkage studies but a poor correlation with results from genome-wide association studies
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