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Search Results: 1 - 10 of 195533 matches for " Thomas E. Besser "
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Urine from Treated Cattle Drives Selection for Cephalosporin Resistant Escherichia coli in Soil
Murugan Subbiah,Devendra H. Shah,Thomas E. Besser,Jeffrey L. Ullman,Douglas R. Call
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0048919
Abstract: The U.S. Food and Drug Administration recently issued new rules for using ceftiofur in food animals in part because of an increasing prevalence of enteric bacteria that are resistant to 3rd-generation cephalosporins. Parenteral ceftiofur treatment, however, has limited effects on enteric bacteria so we tested the hypothesis that excreted ceftiofur metabolites exert significant selection pressure for ceftiofur-resistant Escherichia coli in soil. Test matrices were prepared by mixing soil with bovine feces and adding urine containing ceftiofur metabolites (CFM) (0 ppm, ~50 ppm and ~100 ppm). Matrices were incubated at 23°C or 4°C for variable periods of time after which residual CFM was quantified using a bioassay. BlaCMY-2 plasmid-bearing ceftiofur resistant (cefR) E. coli and one-month old calves were used to study the selection effects of CFM and transmission of cefR bacteria from the environment back to animals. Our studies showed that urinary CFM (~13 ppm final concentration) is biologically degraded in soil within 2.7 days at 23°C, but persists up to 23.3 days at 4°C. Even short-term persistence in soil provides a >1 log10 advantage to resistant E. coli populations, resulting in significantly prolonged persistence of these bacteria in the soil (~two months). We further show that resistant strains readily colonize calves by contact with contaminated bedding and without antibiotic selection pressure. Ceftiofur metabolites in urine amplify resistant E. coli populations and, if applicable to field conditions, this effect is far more compelling than reported selection in vivo after parenteral administration of ceftiofur. Because ceftiofur degradation is temperature dependent, these compounds may accumulate during colder months and this could further enhance selection as seasonal temperatures increase. If cost-effective engineered solutions can be developed to limit ex vivo selection, this may limit proliferation for ceftiofur resistant enteric bacteria while preserving the ability to use this important antibiotic in food animal production.
Carriage of stx2a Differentiates Clinical and Bovine-Biased Strains of Escherichia coli O157
Smriti Shringi, Carrie Schmidt, Kaya Katherine, Kelly A. Brayton, Dale D. Hancock, Thomas E. Besser
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0051572
Abstract: Background Shiga toxin (Stx) are cardinal virulence factors of enterohemorrhagic E. coli O157:H7 (EHEC O157). The gene content and genomic insertion sites of Stx-associated bacteriophages differentiate clinical genotypes of EHEC O157 (CG, typical of clinical isolates) from bovine-biased genotypes (BBG, rarely identified among clinical isolates). This project was designed to identify bacteriophage-mediated differences that may affect the virulence of CG and BBG. Methods Stx-associated bacteriophage differences were identified by whole genome optical scans and characterized among >400 EHEC O157 clinical and cattle isolates by PCR. Results Optical restriction maps of BBG strains consistently differed from those of CG strains only in the chromosomal insertion sites of Stx2-associated bacteriophages. Multiplex PCRs (stx1, stx2a, and stx2c as well as Stx-associated bacteriophage - chromosomal insertion site junctions) revealed four CG and three BBG that accounted for >90% of isolates. All BBG contained stx2c and Stx2c-associated bacteriophage – sbcB junctions. All CG contained stx2a and Stx2a-associated bacteriophage junctions in wrbA or argW. Conclusions Presence or absence of stx2a (or another product encoded by the Stx2a-associated bacteriophage) is a parsimonious explanation for differential virulence of BBG and CG, as reflected in the distributions of these genotypes in humans and in the cattle reservoir.
An Individual-Based Model of Transmission of Resistant Bacteria in a Veterinary Teaching Hospital
Neeraj Suthar, Sandip Roy, Douglas R. Call, Thomas E. Besser, Margaret A. Davis
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0098589
Abstract: Veterinary nosocomial infections caused by antibiotic resistant bacteria cause increased morbidity, higher cost and length of treatment and increased zoonotic risk because of the difficulty in treating them. In this study, an individual-based model was developed to investigate the effects of movements of canine patients among ten areas (transmission points) within a veterinary teaching hospital, and the effects of these movements on transmission of antibiotic susceptible and resistant pathogens. The model simulates contamination of transmission points, healthcare workers, and patients as well as the effects of decontamination of transmission points, disinfection of healthcare workers, and antibiotic treatments of canine patients. The model was parameterized using data obtained from hospital records, information obtained by interviews with hospital staff, and the published literature. The model suggested that transmission resulting from contact with healthcare workers was common, and that certain transmission points (housing wards, diagnostics room, and the intensive care unit) presented higher risk for transmission than others (lobby and surgery). Sensitivity analyses using a range of parameter values demonstrated that the risk of acquisition of colonization by resistant pathogens decreased with shorter patient hospital stays (P<0.0001), more frequent decontamination of transmission points and disinfection of healthcare workers (P<0.0001) and better compliance of healthcare workers with hygiene practices (P<0.0001). More frequent decontamination of heavily trafficked transmission points was especially effective at reducing transmission of the model pathogen.
Use of Exposure History to Identify Patterns of Immunity to Pneumonia in Bighorn Sheep (Ovis canadensis)
Raina K. Plowright, Kezia Manlove, E. Frances Cassirer, Paul C. Cross, Thomas E. Besser, Peter J. Hudson
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0061919
Abstract: Individual host immune responses to infectious agents drive epidemic behavior and are therefore central to understanding and controlling infectious diseases. However, important features of individual immune responses, such as the strength and longevity of immunity, can be challenging to characterize, particularly if they cannot be replicated or controlled in captive environments. Our research on bighorn sheep pneumonia elucidates how individual bighorn sheep respond to infection with pneumonia pathogens by examining the relationship between exposure history and survival in situ. Pneumonia is a poorly understood disease that has impeded the recovery of bighorn sheep (Ovis canadensis) following their widespread extirpation in the 1900s. We analyzed the effects of pneumonia-exposure history on survival of 388 radio-collared adults and 753 ewe-lamb pairs. Results from Cox proportional hazards models suggested that surviving ewes develop protective immunity after exposure, but previous exposure in ewes does not protect their lambs during pneumonia outbreaks. Paradoxically, multiple exposures of ewes to pneumonia were associated with diminished survival of their offspring during pneumonia outbreaks. Although there was support for waning and boosting immunity in ewes, models with consistent immunizing exposure were similarly supported. Translocated animals that had not previously been exposed were more likely to die of pneumonia than residents. These results suggest that pneumonia in bighorn sheep can lead to aging populations of immune adults with limited recruitment. Recovery is unlikely to be enhanced by translocating na?ve healthy animals into or near populations infected with pneumonia pathogens.
Safety and Immunogenicity of a Mycoplasma ovipneumoniae Bacterin for Domestic Sheep (Ovis aries)
Jessie C. Ziegler, Kevin K. Lahmers, George M. Barrington, Steven M. Parish, Katherine Kilzer, Katherine Baker, Thomas E. Besser
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0095698
Abstract: Background Mortality from epizootic pneumonia is hindering re-establishment of bighorn sheep populations in western North America. Mycoplasma ovipneumoniae, a primary agent of this disease, is frequently carried asymptomatically by the domestic sheep and goats that constitute the reservoir of this agent for transmission to bighorn sheep. Our long-term objective is to reduce the risk of M. ovipneumoniae infection of bighorn sheep; one approach to this objective is to control the pathogen in its reservoir hosts. Methods The safety and immunogenicity of M. ovipneumoniae for domestic sheep was evaluated in three experimental immunization protocols: 1) live M. ovipneumoniae (50 ug protein); 2) killed M. ovipneumoniae (50 ug whole cell protein) in oil adjuvant; and 3) killed M. ovipneumoniae (250 ug whole cell protein) in oil adjuvant. Immunogenicity was assessed by two serum antibody measures: competitive enzyme-linked immunosorbent assay (cELISA) (experiments 1–3) and serum growth inhibition (Experiment 3). Passive immunogenicity was also assessed in the third experiment using the same assays applied to blood samples obtained from the lambs of immunized ewes. Results and Conclusions Adverse reactions to immunization were generally minor, but local reactions were regularly observed at immunization sites with bacterins in oil adjuvants. No evidence of M. ovipneumoniae specific antibody responses were observed in the first or second experiments and no resistance to colonization was observed in the first experiment. However, the ewes in the third experiment developed strong cELISA serum antibody responses and significant serum M. ovipneumoniae inhibition activity, and these responses were passively transferred to their lambs. The results of these trials indicate that immunization with relatively large antigenic mass combined with an adjuvant is capable of inducing strong active antibody responses in ewes and passively immunizing lambs.
Whole-Genome Comparison of Two Campylobacter jejuni Isolates of the Same Sequence Type Reveals Multiple Loci of Different Ancestral Lineage
Patrick J. Biggs, Paul Fearnhead, Grant Hotter, Vathsala Mohan, Julie Collins-Emerson, Errol Kwan, Thomas E. Besser, Adrian Cookson, Philip E. Carter, Nigel P. French
PLOS ONE , 2011, DOI: 10.1371/journal.pone.0027121
Abstract: Campylobacter jejuni ST-474 is the most important human enteric pathogen in New Zealand, and yet this genotype is rarely found elsewhere in the world. Insight into the evolution of this organism was gained by a whole genome comparison of two ST-474, flaA SVR-14 isolates and other available C. jejuni isolates and genomes. The two isolates were collected from different sources, human (H22082) and retail poultry (P110b), at the same time and from the same geographical location. Solexa sequencing of each isolate resulted in 1.659 Mb (H22082) and 1.656 Mb (P110b) of assembled sequences within 28 (H22082) and 29 (P110b) contigs. We analysed 1502 genes for which we had sequences within both ST-474 isolates and within at least one of 11 C. jejuni reference genomes. Although 94.5% of genes were identical between the two ST-474 isolates, we identified 83 genes that differed by at least one nucleotide, including 55 genes with non-synonymous substitutions. These covered 101 kb and contained 672 point differences. We inferred that 22 (3.3%) of these differences were due to mutation and 650 (96.7%) were imported via recombination. Our analysis estimated 38 recombinant breakpoints within these 83 genes, which correspond to recombination events affecting at least 19 loci regions and gives a tract length estimate of 2 kb. This includes a 12 kb region displaying non-homologous recombination in one of the ST-474 genomes, with the insertion of two genes, including ykgC, a putative oxidoreductase, and a conserved hypothetical protein of unknown function. Furthermore, our analysis indicates that the source of this recombined DNA is more likely to have come from C. jejuni strains that are more closely related to ST-474. This suggests that the rates of recombination and mutation are similar in order of magnitude, but that recombination has been much more important for generating divergence between the two ST-474 isolates.
miR-1/133a Clusters Cooperatively Specify the Cardiomyogenic Lineage by Adjustment of Myocardin Levels during Embryonic Heart Development
Katharina Wystub,Johannes Besser,Angela Bachmann,Thomas Boettger ,Thomas Braun
PLOS Genetics , 2013, DOI: 10.1371/journal.pgen.1003793
Abstract: miRNAs are small RNAs directing many developmental processes by posttranscriptional regulation of protein-coding genes. We uncovered a new role for miR-1-1/133a-2 and miR-1-2/133a-1 clusters in the specification of embryonic cardiomyocytes allowing transition from an immature state characterized by expression of smooth muscle (SM) genes to a more mature fetal phenotype. Concomitant knockout of miR-1-1/133a-2 and miR-1-2/133a-1 released suppression of the transcriptional co-activator myocardin, a major regulator of SM gene expression, but not of its binding partner SRF. Overexpression of myocardin in the embryonic heart essentially recapitulated the miR-1/133a mutant phenotype at the molecular level, arresting embryonic cardiomyocytes in an immature state. Interestingly, the majority of postulated miR-1/133a targets was not altered in double mutant mice, indicating that the ability of miR-1/133a to suppress target molecules strongly depends on the cellular context. Finally, we show that myocardin positively regulates expression of miR-1/133a, thus constituting a negative feedback loop that is essential for early cardiac development.
A case study of HF radar spectra and 630.0 nm auroral emission in the pre-midnight sector
M. Lester,S. E. Milan,V. Besser,R. Smith
Annales Geophysicae (ANGEO) , 2003,
Abstract: A comparison of HF radar backscatter observed by the CUTLASS Finland radar, meridian scanning photometer data from Longyearbyen, magnetic field variations from IMAGE stations, and particle precipitation measured by the DMSP F12 spacecraft is presented. The interval under discussion occurred in the pre-midnight local time sector, during a period of weakly northward interplanetary magnetic field. A region of HF backscatter, typically 8 degrees wide, occurred in the field of view of the CUTLASS Finland radar. A well defined gradient in the spectral width parameter was present, with mainly low (< 200 m s - 1 ) spectral widths in the lower latitude part of the scatter and predominantly large (> 200 ms - 1 ) spectral widths in the higher latitude part. The relationship between the spectral width and the red line (630.0 nm) emission measured by the meridian scanning photometer is considered. The poleward border of the red line emission, which has, in the past, been proposed as being representative of the polar cap boundary, was co-located to within 1° of magnetic latitude with the gradient in spectral width for part of the interval. Statistically, large spectral widths occurred poleward of the red line emission, while small spectral widths occurred within or equatorward of the red line emission. Near simultaneous DMSP particle observations in the 20 eV to 20 keV range indicate that the poleward border of the red line emission and the gradient in spectral width occurred at the same latitude as the transition from auroral oval to polar rain particle energies. We conclude that the large spectral widths were not caused by particle precipitation associated with the auroral oval. There were two periods of special interest when the relationship between the red line and the spectral width broke down. The first of these happened during enhanced red line and green line (557.7 nm) emission, with a drop out of the radar scatter and an enhanced, narrow westward electrojet. We conclude that this event was a magnetospheric substorm occurring at much higher than usual latitudes. The second period of special interest happened when equatorward moving bands of large spectral width occurred within the region of scatter. Up to 4 of these bands were present during an interval of 100 minutes. Associated with these narrow bands of large spectral width were narrow channels of enhanced westward ion velocities. We conclude that these equatorward moving bands of large spectral width may be related to reconnection processes in the tail. The observations demonstrate that the tail continues
p-adic Arakelov theory
Amnon Besser
Mathematics , 2003,
Abstract: We introduce the p-adic analogue of Arakelov intersection theory on arithmetic surfaces. The intersection pairing in an extension of the p-adic height pairing for divisors of degree 0 in the form described by Coleman and Gross. It also uses Coleman integration and is related to work of Colmez on p-adic Green functions. We introduce the p-adic version of a metrized line bundle and define the metric on the determinant of its cohomology in the style of Faltings. It is possible to prove in this theory analogues of the Adjunction formula and the Riemann-Roch formula.
The p-adic height pairings of Coleman-Gross and of Nekovar
Amnon Besser
Mathematics , 2002,
Abstract: We prove that the p-adic height pairing of Nekovar, considered for algebraic curves, gives the p-adic height pairing of Coleman and Gross, defined using Coleman integration.
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