1,720,975 research outputs found
The CDF-type metal efflux protein EmfA is essential for Brucella abortus 2308 resistance to manganese toxicity and is a critical virulence determinant in experimentally-infected mice
No full textDivalent cationic metals are important trace nutrients for all bacteria because metals serve as cofactors for proteins involved in numerous cellular functions. Despite the fact that metals play an essential role in bacterial physiology, metals become harmful to bacteria if accumulated in excess. To prevent metal-induced toxicity, bacteria employ a variety of factors, such as metal-responsive transcriptional regulators and metal efflux proteins, that function to maintain proper intracellular metal homeostasis. The Brucella strains are Gram-negative, pathogenic bacteria that cause the severe febrile zoonotic disease, brucellosis, and these bacteria require the metal manganese for growth and during host infection. While the manganese acquisition protein, MntH, is essential for the capacity of Brucella spp. to maintain sufficient manganese nutrition, the mechanisms by which these bacteria prevent manganese toxicity have not been determined. The studies of this thesis were performed to identify how Brucella spp. cope with manganese toxicity and whether these factors are essential for Brucella virulence
A Wzx-Wzy-like Polysaccharide Biosynthetic Pathway Contributes to Virulence in Brucella abortus 2308 through an Unknown Mechanism
No full textBrucella abortus is an intracellular pathogen that causes spontaneous abortion in cattle and undulant fever in humans. As a member of the a-proteobacteria, B. abortus is closely related to the bacterial species Caulobacter crescentus and Agrobacterium tumefaciens, which have been shown to produce a holdfast and a unipolar polysaccharide (UPP), respectively, at one pole of the bacterial cell. Although little is currently known about exopolysaccharide production and function in Brucella species, recent evidence suggests that these bacteria are capable of producing exopolysaccharides, and with the exception of a flippase gene, B. abortus 2308 carries the genes for a complete UPP biosynthetic pathway.
In A. tumefaciens, UPP can be detected by crystal violet, Congo red, or lectin staining; however, UPP production was not detected in B. abortus 2308 using these assays. UPP production can also be increased in A. tumefaciens by overexpressing the diguanylate cyclase PleD, which regulates intracellular cyclic di-GMP levels, but we were unable to demonstrate that UPP is regulated by cyclic di-GMP in B. abortus 2308.
Nonetheless, upp homologs in B. abortus 2308 are able to restore biofilm production in A. tumefaciens. In A. tumefaciens, knockout mutants of the outer membrane transporter uppC
and the polyisoprenylphosphate hexose-1-phosphate transferase uppE result in strong biofilm phenotypes, wherein the ability of A. tumefaciens to produce a biofilm is nearly abrogated. B. abortus 2308 uppC and uppE homologs restore biofilm production in the respective Agrobacterium upp mutants, indicating that uppC and uppE from B. abortus 2308 produce functional proteins.
A uppCE mutant in B. abortus 2308 also exhibits significant attenuation in mice and an altered intracellular replication profile in cultured murine macrophages. Accordingly, uppCE appears to be required for virulence in B. abortus 2308, although by a currently unknown mechanism. Additional studies will be needed to determine whether B. abortus 2308 produces an authentic UPP as well as define the mechanisms by which the putative upp genes contribute to virulence
Characterization of FtrABCD: a ferrous iron-specific transporter that is required for the virulence of Brucella abortus 2308 in mice
No full textBrucella strains are Gram-negative bacteria that cause abortion and infertility in their natural animal hosts resulting in extensive economic losses. Humans can acquire a chronic, debilitating febrile illness known as brucellosis as the result of contact with infected animals or consumption of their products. The brucellae live mainly inside phagosomal compartments in host macrophages where they struggle to acquire enough of the essential micronutrient iron to meet their physiological needs. Brucella spp. have evolved multiple strategies to overcome iron limitation in their mammalian hosts, including siderophore-dependent ferric iron-specific transport and heme acquisition systems. The work presented in this dissertation characterized a ferrous iron (Fe2+) specific transporter encoded by the genes designated bab2_0837-0840 in the Brucella abortus 2308 genome sequence. This transporter is homologous to the FtrABCD transporter recently described in Bordetella. Interestingly, this transporter is required for the virulence of B. abortus 2308 in experimentally infected mice, supporting the proposition that ferrous iron is a critical iron source for these bacteria in the mammalian host. The iron response regulator (Irr), the predominant iron-responsive regulator in Brucella and the other alpha-proteobacteria, activates the expression of the ftrABCD operon in response to iron deprivation by binding a consensus Irr binding site in the promoter region of these genes. These genes are also activated by exposure to acidic pH, which is important because it potentially allows the brucellae to fine-tune the expression of their iron acquisition genes to adapt to the acidic environment they encounter in the phagosomal compartment of host macrophages, where Fe2+ is thought to be a biologically relevant iron source. The ftr locus is also regulated by the Zn finger protein MucR which belongs to the Ros/MucR family of transcriptional regulators that function as global transcriptional regulators in the [alpha]-proteobacteria. MucR has a secondary role in regulating the expression of the ftr genes in B. abortus 2308 by binding to a region very near to the Irr binding site and the acid-responsive regulatory element in the promoter region of these genes. MucR potentially interacts with Irr and the as yet unidentified acid-responsive transcriptional regulator, thus modulating the capacity of these regulators to bind to their target sites in the promoter region of the ftr locus. This type of secondary regulatory function is consistent with what has described for several MucR-regulated genes in other [alpha]-proteobacteria. In conclusion, the work presented in this dissertation showed that the ferrous iron specific transporter FtrABCD is required for Brucella abortus 2308 to survive and replicate in the host macrophage where Fe2+ is an essential and relevant micronutrient. The regulation of the expression of the ftrABCD genes by Irr, the acid-responsive transcriptional regulator and MucR is important because it potentially allows the brucellae to adapt to the environmental niches they inhabit during their residence in host macrophages
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
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