Species status of Neisseria gonorrhoeae: Evolutionary and epidemiological inferences from multilocus sequence typing

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited - Copyright @ 2007 Bennett et al; licensee BioMed Central Ltd.Background: Various typing methods have been developed for Neisseria gonorrhoeae, but none provide the combination of discrimination, reproducibility, portability, and genetic inference that allows the analysis of all aspects of the epidemiology of this pathogen from a single data set. Multilocus sequence typing (MLST) has been used successfully to characterize the related organisms Neisseria meningitidis and Neisseria lactamica. Here, the same seven locus Neisseria scheme was used to characterize a diverse collection of N. gonorrhoeae isolates to investigate whether this method would allow differentiation among isolates, and to distinguish these three species. Results: A total of 149 gonococcal isolates were typed and submitted to the Neisseria MLST database. Although relatively few (27) polymorphisms were detected among the seven MLST loci, a total of 66 unique allele combinations (sequence types, STs), were observed, a number comparable to that seen among isolate collections of the more diverse meningococcus. Patterns of genetic variation were consistent with high levels of recombination generating this diversity. There was no evidence for geographical structuring among the isolates examined, with isolates collected in Liverpool, UK, showing levels of diversity similar to a global collection of isolates. There was, however, evidence that populations of N. meningitidis, N. gonorrhoeae and N. lactamica were distinct, with little support for frequent genetic recombination among these species, with the sequences from the gdh locus alone grouping the species into distinct clusters. Conclusion: The seven loci Neisseria MLST scheme was readily adapted to N. gonorrhoeae isolates, providing a highly discriminatory typing method. In addition, these data permitted phylogenetic and population genetic inferences to be made, including direct comparisons with N. meningitidis and N. lactamica. Examination of these data demonstrated that alleles were rarely shared among the three species. Analysis of variation at a single locus, gdh, provided a rapid means of identifying misclassified isolates and determining whether mixed cultures were present.This study is funded by the Wellcome Trust and European Unio

Improvement of NADPH bioavailability in Escherichia coli through the use of phosphofructokinase deficient strains

NADPH-dependent reactions play important roles in production of industrially valuable compounds. In this study, we used phosphofructokinase (PFK)-deficient strains to direct fructose-6-phosphate to be oxidized through the pentose phosphate pathway (PPP) to increase NADPH generation. pfkA or pfkB single deletion and double-deletion strains were tested for their ability to produce lycopene. Since lycopene biosynthesis requires many NADPH, levels of lycopene were compared in a set of isogenic strains, with the pfkA single deletion strain showing the highest lycopene yield. Using another NADPH-requiring process, a one-step reduction reaction of 2-chloroacrylate to 2-chloropropionic acid by 2- haloacrylate reductase, the pfkA pfkB double-deletion strain showed the highest yield of 2-chloropropionic acid product. The combined effect of glucose-6-phosphate dehydrogenase overexpression or lactate dehydrogenase deletion with PFK deficiency on NADPH bioavailability was also studied. The results indicated that the flux distribution of fructose-6- phosphate between glycolysis and the pentose phosphate pathway determines the amount of NAPDH available for reductive biosynthesis

Non-Markovian reduced dynamics and entanglement evolution of two coupled spins in a quantum spin environment

The exact quantum dynamics of the reduced density matrix of two coupled spin qubits in a quantum Heisenberg XY spin star environment in the thermodynamic limit at arbitrarily finite temperatures is obtained using a novel operator technique. In this approach, the transformed Hamiltonian becomes effectively Jaynes-Cumming like and thus the analysis is also relevant to cavity quantum electrodynamics. This special operator technique is mathematically simple and physically clear, and allows us to treat systems and environments that could all be strongly coupled mutually and internally. To study their entanglement evolution, the concurrence of the reduced density matrix of the two coupled central spins is also obtained exactly. It is shown that the dynamics of the entanglement depends on the initial state of the system and the coupling strength between the two coupled central spins, the thermal temperature of the spin environment and the interaction between the constituents of the spin environment. We also investigate the effect of detuning which in our model can be controlled by the strength of a locally applied external magnetic field. It is found that the detuning has a significant effect on the entanglement generation between the two spin qubits.Comment: 9 pages (two-coulumn), 6 figures. To appear in Phys. Rev.

Associations between e-cigarette access and smoking and drinking behaviours in teenagers

Background: Public health concerns regarding e-cigarettes and debate on appropriate regulatory responses are focusing on the need to prevent child access to these devices. However, little is currently known about the characteristics of those young people that are accessing e-cigarettes. Methods: Using a cross-sectional survey of 14-17 year old school students in North West England (n = 16,193) we examined associations between e-cigarette access and demographics, conventional smoking behaviours, alcohol consumption, and methods of accessing cigarettes and alcohol. Access to e-cigarettes was identified through a question asking students if they had ever tried or purchased e-cigarettes. Results: One in five participants reported having accessed e-cigarettes (19.2%). Prevalence was highest among\ud smokers (rising to 75.8% in those smoking >5 per day), although 15.8% of teenagers that had accessed e-cigarettes had never smoked conventional cigarettes (v.13.6% being ex-smokers). E-cigarette access was independently associated with male gender, having parents/guardians that smoke and students’ alcohol use. Compared with non-drinkers, teenagers that drank alcohol at least weekly and binge drank were more likely to have accessed e-cigarettes (adjusted odds ratio [AOR] 1.89, P < 0.001), with this association particularly strong among never-smokers (AOR 4.59, P < 0.001). Among drinkers, e-cigarette access was related to: drinking to get drunk, alcohol-related violence, consumption of spirits; self-purchase of alcohol from shops or supermarkets; and accessing alcohol by recruiting adult proxy purchasers outside shops. Conclusions: There is an urgent need for controls on the promotion and sale of e-cigarettes to children. Findings suggest that e-cigarettes are being accessed by teenagers more for experimentation than smoking cessation. Those most likely to access e-cigarettes may already be familiar with illicit methods of accessing age-restricted substances

Influence of an external magnetic field on the decoherence of a central spin coupled to an antiferromagnetic environment

Using the spin wave approximation, we study the decoherence dynamics of a central spin coupled to an antiferromagnetic environment under the application of an external global magnetic field. The external magnetic field affects the decoherence process through its effect on the antiferromagnetic environment. It is shown explicitly that the decoherence factor which displays a Gaussian decay with time depends on the strength of the external magnetic field and the crystal anisotropy field in the antiferromagnetic environment. When the values of the external magnetic field is increased to the critical field point at which the spin-flop transition (a first-order quantum phase transition) happens in the antiferromagnetic environment, the decoherence of the central spin reaches its highest point. This result is consistent with several recent quantum phase transition witness studies. The influences of the environmental temperature on the decoherence behavior of the central spin are also investigated.Comment: 29 preprint pages, 4 figures, to appear in New Journal of Physic

Genetic and metabolic engineering

Recent advances in molecular biology techniques, analytical methods and mathematical tools have led to a growing interest in using metabolic engineering to redirect metabolic fluxes for industrial and medical purposes. Metabolic engineering is referred to as the directed improvement of cellular properties through the modification of specific biochemical reactions or the introduction of new ones, with the use of recombinant DNA technology (Stephanopoulos, 1999). This multidisciplinary field draws principles from chemical engineering, biochemistry, molecular and cell biology, and computational sciences. The aim of this article is to give an overview of the various strategies and tools available for metabolic engineers and to review some of the recent work that has been conducted in our laboratories in the metabolic engineering area

Plasticity of the human visual system after retinal gene therapy in patients with Leber's congenital amaurosis.

Much of our knowledge of the mechanisms underlying plasticity in the visual cortex in response to visual impairment, vision restoration, and environmental interactions comes from animal studies. We evaluated human brain plasticity in a group of patients with Leber's congenital amaurosis (LCA), who regained vision through gene therapy. Using non-invasive multimodal neuroimaging methods, we demonstrated that reversing blindness with gene therapy promoted long-term structural plasticity in the visual pathways emanating from the treated retina of LCA patients. The data revealed improvements and normalization along the visual fibers corresponding to the site of retinal injection of the gene therapy vector carrying the therapeutic gene in the treated eye compared to the visual pathway for the untreated eye of LCA patients. After gene therapy, the primary visual pathways (for example, geniculostriate fibers) in the treated retina were similar to those of sighted control subjects, whereas the primary visual pathways of the untreated retina continued to deteriorate. Our results suggest that visual experience, enhanced by gene therapy, may be responsible for the reorganization and maturation of synaptic connectivity in the visual pathways of the treated eye in LCA patients. The interactions between the eye and the brain enabled improved and sustained long-term visual function in patients with LCA after gene therapy

Validation and Use of 22Na Turnover to Measure Food Intake in Free-Ranging Lizards

As the food intake of free-ranging animals has proved to be difficult to measure by traditional means, the feasibility of using radioactive Na to measure food consumption in a small scincid lizard (Lampropholis guichenoti) was assessed. This technique has previously been used only for several species of mammal. A significant relationship between food intake and Na turnover was found in the laboratory, with Na turnover underestimating intake by 7.6%. The food intake of free-ranging members of a field population was estimated by 22Na turnover to be 9.55, 0.65, 9.39 and 13.75 mg dry weight (day)-1 during autumn, winter, spring and summer respectively. Estimates of assimilated and expended energy from these food intake values agree closely with data reported for other lizards using alternative techniques. This study also describes the technical innovations which were necessary to study lizards weighing less than 1 g; and it suggests that 22Na can provide an easy, reliable and inexpensive means of studying the energetics of many free-living animals

Ultra-high field imaging, plasma markers and autopsy data uncover a specific rostral locus coeruleus vulnerability to hyperphosphorylated tau

Autopsy data indicate that the locus coeruleus (LC) is one of the first sites in the brain to accumulate hyperphosphorylated tau pathology, with the rostral part possibly being more vulnerable in the earlier stages of the disease. Taking advantage of recent developments in ultra-high field (7 T) imaging, we investigated whether imaging measures of the LC also reveal a specific anatomic correlation with tau using novel plasma biomarkers of different species of hyperphosphorylated tau, how early in adulthood these associations can be detected and if are associated with worse cognitive performance. To validate the anatomic correlations, we tested if a rostro-caudal gradient in tau pathology is also detected at autopsy in data from the Rush Memory and Aging Project (MAP). We found that higher plasma measures of phosphorylated tau, in particular ptau231, correlated negatively with dorso-rostral LC integrity, whereas correlations for neurodegenerative plasma markers (neurofilament light, total tau) were scattered throughout the LC including middle to caudal sections. In contrast, the plasma Aβ42/40 ratio, associated with brain amyloidosis, did not correlate with LC integrity. These findings were specific to the rostral LC and not observed when using the entire LC or the hippocampus. Furthermore, in the MAP data, we observed higher rostral than caudal tangle density in the LC, independent of the disease stage. The in vivo LC-phosphorylated tau correlations became significant from midlife, with the earliest effect for ptau231, starting at about age 55. Finally, interactions between lower rostral LC integrity and higher ptau231 concentrations predicted lower cognitive performance. Together, these findings demonstrate a specific rostral vulnerability to early phosphorylated tau species that can be detected with dedicated magnetic resonance imaging measures, highlighting the promise of LC imaging as an early marker of AD-related processes