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Search Results: 1 - 10 of 149776 matches for " Douglas F. Browning "
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Silencing of DNase Colicin E8 Gene Expression by a Complex Nucleoprotein Assembly Ensures Timely Colicin Induction
Simona Kamen?ek?,Douglas F. Browning,Zdravko Podlesek?,Stephen J. W. Busby?,Darja ?gur-Bertok?,Matej Butala
PLOS Genetics , 2015, DOI: 10.1371/journal.pgen.1005354
Abstract: Colicins are plasmid-encoded narrow spectrum antibiotics that are synthesized by strains of Escherichia coli and govern intraspecies competition. In a previous report, we demonstrated that the global transcriptional factor IscR, co dependently with the master regulator of the DNA damage response, LexA, delays induction of the pore forming colicin genes after SOS induction. Here we show that IscR is not involved in the regulation of nuclease colicins, but that the AsnC protein is. We report that AsnC, in concert with LexA, is the key controller of the temporal induction of the DNA degrading colicin E8 gene (cea8), after DNA damage. We demonstrate that a large AsnC nucleosome-like structure, in conjunction with two LexA molecules, prevent cea8 transcription initiation and that AsnC binding activity is directly modulated by L asparagine. We show that L-asparagine is an environmental factor that has a marked impact on cea8 promoter regulation. Our results show that AsnC also modulates the expression of several other DNase and RNase colicin genes but does not substantially affect pore-forming colicin K gene expression. We propose that selection pressure has “chosen” highly conserved regulators to control colicin expression in E. coli strains, enabling similar colicin gene silencing among bacteria upon exchange of colicinogenic plasmids.
Mutational and Topological Analysis of the Escherichia coli BamA Protein
Douglas F. Browning, Sophie A. Matthews, Amanda E. Rossiter, Yanina R. Sevastsyanovich, Mark Jeeves, Jessica L. Mason, Timothy J. Wells, Catherine A. Wardius, Timothy J. Knowles, Adam F. Cunningham, Vassiliy N. Bavro, Michael Overduin, Ian R. Henderson
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0084512
Abstract: The multi-protein β-barrel assembly machine (BAM) of Escherichia coli is responsible for the folding and insertion of β-barrel containing integral outer membrane proteins (OMPs) into the bacterial outer membrane. An essential component of this complex is the BamA protein, which binds unfolded β-barrel precursors via the five polypeptide transport-associated (POTRA) domains in its N-terminus. The C-terminus of BamA contains a β-barrel domain, which tethers BamA to the outer membrane and is also thought to be involved in OMP insertion. Here we mutagenize BamA using linker scanning mutagenesis and demonstrate that all five POTRA domains are essential for BamA protein function in our experimental system. Furthermore, we generate a homology based model of the BamA β-barrel and test our model using insertion mutagenesis, deletion analysis and immunofluorescence to identify β-strands, periplasmic turns and extracellular loops. We show that the surface-exposed loops of the BamA β-barrel are essential.
Genotypic and Phenotypic Characterisation of Enteroaggregative Escherichia coli from Children in Rio de Janeiro, Brazil
Fernanda L. S. Fran?a, Timothy J. Wells, Douglas F. Browning, Raquel Tayar Nogueira, Felipe Silva Sarges, Ana Claudia Pereira, Adam F. Cunningham, Kely Lucheze, Ana Claudia Paula Rosa, Ian R. Henderson, Maria das Gra?as de Luna
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0069971
Abstract: Enteroaggregative Escherichia coli (EAEC) is a significant cause of diarrhoeal illness in both children and adults. Genetic heterogeneity and recovery of EAEC strains from both healthy and diseased individuals complicates our understanding of EAEC pathogenesis. We wished to establish if genetic or phenotypic attributes could be used to distinguish between strains asymptomatically colonising healthy individuals and those which cause disease. Genotypic screening of a collection of twenty four EAEC isolates from children with and without diarrhoea revealed no significant differences in the repertoire of putative virulence factors present in either group of strains. In contrast, EAEC strains from phylogroup A were more strongly associated with asymptomatic groups whereas strains from phylogroup D were more associated with cases of diarrhoea. Phenotypic screening revealed no differences in the ability of strains from either cohort of children to form biofilms, to adhere to and invade cells in tissue culture or to cause disease in the Caenorhabditis elegans model of infection. However, the latter assay did reveal significant reduction in nematode killing rates when specific virulence factors were deleted from human pathogenic strains. Our results suggest that current models of infection are not useful for distinguishing avirulent from pathogenic strains of EAEC but can be useful in studying the effect of specific virulence factors.
Genes Found Essential in Other Mycoplasmas Are Dispensable in Mycoplasma bovis
Shukriti Sharma, Philip F. Markham, Glenn F. Browning
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0097100
Abstract: Mycoplasmas are regarded to be useful models for studying the minimum genetic complement required for independent survival of an organism. Mycoplasma bovis is a globally distributed pathogen causing pneumonia, mastitis, arthritis, otitis media and reproductive tract disease, and genome sequences of three strains, the type strain PG45 and two strains isolated in China, have been published. In this study, several Tn4001 based transposon constructs were generated and used to create a M. bovis PG45 insertional mutant library. Direct genome sequencing of 319 independent insertions detected disruptions in 129 genes in M. bovis, 48 of which had homologues in Mycoplasma mycoides subspecies mycoides SC and 99 of which had homologues in Mycoplasma agalactiae. Sixteen genes found to be essential in previous studies on other mycoplasma species were found to be dispensable. Five of these genes have previously been predicted to be part of the core set of 153 essential genes in mycoplasmas. Thus this study has extended the list of non-essential genes of mycoplasmas from that previously generated by studies in other species.
Doorstop: Text-Based Requirements Management Using Version Control  [PDF]
Jace Browning, Robert Adams
Journal of Software Engineering and Applications (JSEA) , 2014, DOI: 10.4236/jsea.2014.73020
Abstract:

Effectively managing the requirements and traceability in a complex software project can be a challenging task. Many tools exist to support the initial creation and management of changes to text-based requirements. The most popular commercial solutions use a centralized server to host a database with a front-end desktop or web interface. Some downsides to this approach include user interface bloat, server costs, and an inherent disconnection from the project’s source files. To provide an alternative to traditional requirements management, Doorstop was created as a tool to allow requirements to be stored as text files in version control. This solution allows a project to utilize its existing development tools to manage versions of the requirements using a lightweight, developer-friendly interface.

Stochastic Reservoir Systems with Different Assumptions for Storage Losses  [PDF]
Carter Browning, Hillel Kumin
American Journal of Operations Research (AJOR) , 2016, DOI: 10.4236/ajor.2016.65038
Abstract: Moran considered a dam whose inflow in a given interval of time is a continuous random variable. He then developed integral equations for the probabilities of emptiness and overflow. These equations are difficult to solve numerically; thus, approximations have been proposed that discretize the input. In this paper, extensions are considered for storage systems with different assumptions for storage losses. We also develop discrete approximations for the probabilities of emptiness and overflow.
Direct observation of nm-scale Mg- and B-oxide phases at grain boundaries in MgB2
R. F. Klie,J. C. Idrobo,N. D. Browning
Physics , 2001, DOI: 10.1063/1.1404127
Abstract: Here we describe the results of an atomic resolution study of the structure and composition of both the interior of the grains, and the grain boundaries in polycrystalline MgB2. We find that there is no oxygen within the bulk of the grains but significant oxygen enrichment at the grain boundaries. The majority of grain boundaries contain BOx phases smaller than the coherence length, while others contain larger areas of MgO sandwiched between BOx layers. Such results naturally explain the differences in connectivity between the grains observed by other techniques.
Thermal and non-thermal emission from reconnecting twisted coronal loops
R. F. Pinto,M. Gordovskyy,P. K. Browning,N. Vilmer
Physics , 2015,
Abstract: Twisted magnetic fields should be ubiquitous in flare-producing active regions where the magnetic fields are strongly non-potential. It has been shown that reconnection in helical magnetic coronal loops results in plasma heating and particle acceleration distributed within a large volume, including the lower coronal and chromospheric sections of the loops. This scenario can be an alternative to the standard flare model, where particles are accelerated only in a small volume located in the upper corona. We use a combination of MHD simulations and test-particle methods, which describe the development of kink instability and magnetic reconnection in twisted coronal loops using resistive compressible MHD, and incorporate atmospheric stratification and large-scale loop curvature. The resulting distributions of hot plasma let us estimate thermal X-ray emission intensities. The electric and magnetic fields obtained are used to calculate electron trajectories using the guiding-centre approximation. These trajectories combined with the MHD plasma density distributions let us deduce synthetic HXR bremsstrahlung intensities. Our simulations emphasise that the geometry of the emission patterns produced by hot plasma in flaring twisted coronal loops can differ from the actual geometry of the underlying magnetic fields. The twist angles revealed by the emission threads (SXR) are consistently lower than the field-line twist present at the onset of the kink-instability. HXR emission due to the interaction of energetic electrons with the stratified background are concentrated at the loop foot-points in these simulations, even though the electrons are accelerated everywhere within the coronal volume of the loop. The maximum of HXR emission consistently precedes that of SXR emission, with the HXR light-curve being approximately proportional to the temporal derivative of the SXR light-curve.
Familial risks of breast cancer
Douglas F Easton
Breast Cancer Research , 2002, DOI: 10.1186/bcr448
Abstract: The increased risk of breast cancer among women with a family history of the disease is one of the oldest established facts about the disease. This familial aggregation has been the inspiration for studies to identify breast cancer susceptibility genes that have borne fruit over the past decade, and has been the basis for defining high-risk groups for intervention studies (e.g. with tamoxifen). Yet despite the fact that questions about family history are asked in almost every epidemiological study of breast cancer, some important questions about the quantitative relationship between family history relationship have not been answered with precision. Among these questions are the magnitude of the risk according to the age of the women and the age of their affected relative(s), the precise effect of numbers and types of affected relatives, and the joint effects of family history and other known risk factors.Since only ~10–15% of women with breast cancer typically report a family history of breast cancer, individual epidemiological studies have not had the power to answer these questions precisely. The recent analysis by the Collaborative Group on Hormonal Factors in Breast Cancer [1] goes a long way toward resolving some of these uncertainties. This group has brought together data from 52 studies, originally to evaluate the effects of oral contraceptives and hormone replacement therapy. In the current overview, the group examine risks according to family history of breast cancer in a first-degree relative in over 58,000 cases and in nearly 102,000 controls.The main results from the overview [1] are straightforward to summarise. The results of the study are mainly expressed in terms of the risk ratio (or relative risk) of breast cancer associated with a family history; that is, the ratio of the incidence rate of breast cancer in relatives of breast cancer cases to the incidence in the relatives of controls. These risk ratios were estimated from the case-control studies
How many more breast cancer predisposition genes are there?
Douglas F Easton
Breast Cancer Research , 1999, DOI: 10.1186/bcr6
Abstract: Of the five genes that are, beyond any reasonable doubt, breast cancer predisposition genes, the BRCA1 and BRCA2 genes are the most important numerically (Table 1). Mutations in these genes, which cause high risks of breast and ovarian cancer, account for almost all the multiple case breast-ovarian cancer families, and probably around 2% of breast cancer cases overall [4,5]. Germline mutations in the TP53 gene predispose to a spectrum of cancers known as the Li-Fraumeni syndrome, including childhood sarcomas and brain tumours, as well as early-onset breast cancer [2]; and germline mutations in the PTEN gene are responsible for Cowdens syndrome, of which breast cancer is a major feature [6]. Mutations in a fifth gene, the androgen receptor gene, are known to pre-dispose to breast cancer in men [7].In addition to the five genes mentioned above, there is good, but not conclusive, evidence for two others. Female relatives of ataxia-telangiectasia patients have been shown in a number of studies [8,9] to be at increased risk of breast cancer (and perhaps of some other cancers), suggesting that heterozygous carriers of mutations in the ataxia-telangiectasia gene, ATM, are at increased risk of breast cancer. The results from different studies are reasonably consistent, and are confirmed by direct observation of haplotype sharing in breast cancer cases in relatives of ataxia-telangiectasia patients [10]. The residual doubt lies in the fact that, to date, no studies have demonstrated this association in breast cancer case-control studies [11]. There is also evidence that carriers of a certain class of rare alleles of the HRAS1 minisatellite locus are at increased risk of breast (and other) cancers, the relative risk being approximately two-fold [12]. The doubts that surround this association are that the typing of this locus is technically difficult, and has not been attempted on a sufficiently number of large case-control studies to be really convincing, and that the mechani
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