1,721,004 research outputs found
Staphylococcus aureus Sequences from Osteomyelitic Specimens of a Pathological Bone Collection from Pre-Antibiotic Times
Get PDFStaphylococcus aureus is a major pathogen causing osteomyelitis, amongst other diseases, and its methicillin-resistant form (MRSA) in particular poses a huge threat to public health. To increase our knowledge of the origin and evolution of S. aureus, genetic studies of historical microorganisms may be beneficial. Thus, the aim of this study was to investigate whether osteomyelitic skeletal material (autopsy specimens collected from the mid 19th century until the 1920s) is suitable for detecting historical S. aureus DNA sequences. We established a PCR-based analysis system targeting two specific genes of S. aureus (nuc and fib). We successfully amplified the historical S. aureus nuc and fib sequences for six and seven pre-antibiotic, osteomyelitic bone specimens, respectively. These results encourage further investigations of historical S. aureus genomes that may increase our understanding of pathogen evolution in relation to anthropogenically introduced antibiotics
Penicillin-binding proteins in Staphylococcus aureus - THE or ONE key to β-lactam resistance evolution?
Get PDFZur Untersuchung alternativer genetischer Determinanten, die eine β-Laktam-Resistenz verursachen, wurden vergleichende, genomische Analysen sowie genomweite Assoziationsstudien (GWAS) verwendet, um genetische Polymorphismen zu ermitteln, die mit dem MRLM (Methicillin-resistent, lacking mec) -Phänotyp in klinischen S. aureus Stämmen in Verbindung stehen. Zu diesem Zweck wurde eine repräsentative Stammsammlung aus 141 MRLM Isolaten und 142 genetisch eng verwandten, Methicillin-empfindlichen Kontrollstämmen zusammengestellt. Die Presence/Absence-basierte SCOARY GWAS Analyse konnte Mutationen im Phosphodiesterase-Gen gdpP signifikant mit dem MRLM-Phänotyp assoziieren. 131 MRLM Isolate (92,9 %) trugen gdpP-Mutationen, die zu Trunkierungen, Insertionen, Deletionen und Aminosäuresubstitutionen führten. Darüber hinaus bestätigte eine Gen-Enrichment Analyse, dass das gdpP Gen in MRLM-Stämmen im Durchschnitt 4,6-mal häufiger mutiert war als in MSSA Kontrollen. Die Mutationen in gdpP hatten keine Auswirkungen auf die Transkriptionslevel von pbp4, es konnten jedoch verringerte Zellgrößen bei MRLM Isolaten nachgewiesen werden. Vergleichende SNP-Analysen der nativen pbp1-4-Gene zeigten außerdem 57 verschiedene Aminosäuresubstitutionen in 44 Isolaten (31,2 %), die ausschließlich in MRLM-Stämmen vorkamen. Bei zwei weiteren Isolaten wurden Deletionen im pbp4-Promotor festgestellt, die bei diesen Isolaten zu einer 15-fachen bzw. 7,5-fachen Erhöhung der Transkription von pbp4 führten. Im zweiten Teil der Arbeit wurde ein Ausbruchsszenario mit MRLM Isolaten analysiert. Es wurden insgesamt neun S. aureus-Stämme (MRLM (n=6); MSSA (n=3)) untersucht, die bei vier Frühgeborenen während eines routinemäßigen Nasenscreenings auf der neonatalen Intensivstation (NICU) eines Krankenhauses in Nordrhein-Westfalen isoliert wurden. Alle Isolate wurden dem spa-Typen t3338, dem Multi-Locus-Sequenz-Typen (MLST) ST7 und dem core-Genom MLST (cgMLST) Komplex-Typen CT20916 zugeordnet. Sie unterschieden sich voneinander in maximal 8 der 2249 genomischen Loci, die in die cgMLST-Analyse einbezogen wurden, was auf einen gemeinsamen Ursprung der Isolate hinweist. Sechs Isolate zeigten erhöhte MHKs für Oxacillin (MHK ≥ 2 mg/L) und Cefoxitin (MHK > 4 mg/L), wurden jedoch in der PCR negativ auf mec-Determinanten getestet. Fünf der MRLM Isolate hatten unterschiedliche Mutationen in gdpP, was darauf hindeutet, dass sich diese Polymorphismen bei einzelnen Patienten unabhängig voneinander entwickelt hatten und dass das ursprüngliche Indexisolat wahrscheinlich ein MSSA war. Dieses MSSA Isolat scheint in jedem Patienten unabhängig voneinander unter dem Einfluss eines bisher unbekannten Selektionsdrucks durch verschiedene Mutationen in gdpP eine Resistenz gegen β-Laktame erworben zu haben. Zusammenfassend konnte in dieser Arbeit gezeigt werden, dass Mutationen in gdpP einen klinisch relevanten Mechanismus für β-Laktam-Resistenz in MRLM Isolaten darstellen. Diese Beobachtung ist von besonderer klinischer Relevanz, da MRLM leicht als MSSA fehlklassifiziert werden, was zu einer unbemerkten Ausbreitung von β-Laktam-resistenten Isolaten und anschließendem Therapieversagen führen kann.To investigate alternative genetic determinants causing β-lactam resistance, comparative genomic analyses and genome-wide association studies (GWAS) were used to identify genetic polymorphisms associated with the MRLM (methicillin-resistant, lacking mec) -phenotype in clinical S. aureus strains. To this end, a representative strain collection was assembled from 141 MRLM isolates and 142 genetically closely related, methicillin-susceptible control strains. The presence/absence-based SCOARY GWAS analysis was able to significantly associate mutations in the phosphodiesterase gene gdpP with the MRLM phenotype. 131 MRLM isolates (92.9 %) carried gdpP mutations resulting in truncations, insertions, deletions, and amino acid substitutions. In addition, a gene-enrichment analysis confirmed that the gdpP gene was mutated on average 4.6-fold more frequently in MRLM strains than in MSSA controls. Mutations in gdpP did not affect pbp4 transcript levels, but decreased cell sizes were detected in MRLM isolates. Comparative SNP analysis of the native pbp1-4 genes also revealed 57 different amino acid substitutions in 44 isolates (31.2 %), that were exclusive to MRLM strains. Deletions in the pbp4 promoter were detected in two other isolates, resulting in a 15-fold and 7.5-fold increase in transcription of pbp4 in these isolates, respectively. In the second part of the work, an outbreak scenario with MRLM isolates was analyzed. A total of nine S. aureus strains (MRLM (n=6); MSSA (n=3)) isolated from four preterm infants during routine nasal screening in the neonatal intensive care unit (NICU) of a hospital in North Rhine-Westphalia were studied. All isolates were assigned to spa type t3338, multi-locus sequence type (MLST) ST7, and core-genome MLST (cgMLST) complex type CT20916. They differed from each other in a maximum of 8 of the 2249 genomic loci included in the cgMLST analysis, indicating a common origin of the isolates. Six isolates showed elevated MICs for oxacillin (MIC ≥ 2 mg/L) and cefoxitin (MIC > 4 mg/L) but were tested negative for mec determinants by PCR. Five of the MRLM isolates showed different mutations in gdpP, suggesting that these polymorphisms had developed independently in the individual patients and that the original index isolate was probably an MSSA. This MSSA isolate appears to have acquired resistance to β-lactams in each patient independently under the influence of a previously unknown selection pressure by different mutations in gdpP. In summary, this work demonstrated that mutations in gdpP represent a clinically relevant mechanism for β-lactam resistance in MRLM isolates. This observation is of particular clinical relevance, as MRLM are easily misclassified as MSSA, which can lead to unnoticed spread of β-lactam-resistant isolates and subsequent treatment failure
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Get PDF“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Get PDFWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Get PDFWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
Emerg Infect Dis
No full textMethicillin-resistant Staphylococcus aureus of clonal lineage ST398 that exhibits related spa types and contains SCCmec elements of types IVa or V has been isolated from colonized and infected humans and companion animals (e.g., dog, pig, horse) in Germany and Austria. Of particular concern is the association of these cases with cases of nosocomial ventilator-associated pneumonia
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