Post-vaccine epidemiology of serotype 3 pneumococci identifies transformation inhibition through prophage-driven alteration of a non-coding RNA

Background: The respiratory pathogen Streptococcus pneumoniae (the pneumococcus) is a genetically diverse bacterium associated with over 101 immunologically distinct polysaccharide capsules (serotypes). Polysaccharide conjugate vaccines (PCVs) have successfully eliminated multiple targeted serotypes, yet the mucoid serotype 3 has persisted despite its inclusion in PCV13. This capsule type is predominantly associated with a single globally disseminated strain, GPSC12 (clonal complex 180). Methods: A genomic epidemiology study combined previous surveillance datasets of serotype 3 pneumococci to analyse the population structure, dynamics, and differences in rates of diversification within GPSC12 during the period of PCV introductions. Transcriptomic analyses, whole genome sequencing, mutagenesis, and electron microscopy were used to characterise the phenotypic impact of loci hypothesised to affect this strain’s evolution. Results: GPSC12 was split into clades by a genomic analysis. Clade I, the most common, rarely underwent transformation, but was typically infected with the prophage ϕOXC141. Prior to the introduction of PCV13, this clade’s composition shifted towards a ϕOXC141-negative subpopulation in a systematically sampled UK collection. In the post-PCV13 era, more rapidly recombining non-Clade I isolates, also ϕOXC141-negative, have risen in prevalence. The low in vitro transformation efficiency of a Clade I isolate could not be fully explained by the ~100-fold reduction attributable to the serotype 3 capsule. Accordingly, prophage ϕOXC141 was found to modify csRNA3, a non-coding RNA that inhibits the induction of transformation. This alteration was identified in ~30% of all pneumococci and was particularly common in the unusually clonal serotype 1 GPSC2 strain. RNA-seq and quantitative reverse transcriptase PCR experiments using a genetically tractable pneumococcus demonstrated the altered csRNA3 was more effective at inhibiting production of the competence-stimulating peptide pheromone. This resulted in a reduction in the induction of competence for transformation. Conclusion: This interference with the quorum sensing needed to induce competence reduces the risk of the prophage being deleted by homologous recombination. Hence the selfish prophage-driven alteration of a regulatory RNA limits cell-cell communication and horizontal gene transfer, complicating the interpretation of post-vaccine population dynamics

Level Up Eco-Friendly Hotel Stay: Guest Power Up and Save Energy with Gamification

Executive Summary Hotel businesses endeavor to achieve successful green practices for long-lasting business success. The key issue is to promote consumers’ willingness to participate in such practices. Despite increased environmental awareness among today’s consumers, a relatively large percentage of consumers hesitate to actively engage with green practices because they are unwilling to sacrifice their comforts and convenience for their paid experience. This report introduces a gamification approach to hotels’ green practices through an investigation of how game components motivate guests’ energy-saving participation. This report finds that the energy-saving game can improve hotel guests’ willingness to save energy and even revisit the hotel. This paper offers fruitful suggestions on using gamification to encourage guests’ energy-saving and revisit behaviors

Survival and Synapse Formation of Transplanted Rat Rods

Isolated rods enzymatically removed from normal adult rat retina have been transplanted to the subretinal space of adult rats with a retinal dystrophy winich has destroyed almost all the photoreceptors. These transplanted rods survive for months after transplantation during which time they form synapses with other retinal cells. Rod spherules with large amounts of synaptic vesicles and synaptic ribbons are found forming discreet contacts with pre- and postsynaptic densities in arrangements closely resembling those seen in the normal retina

Modeling the interrelating effects of plastic deformation and stress on magnetic properties of materials

A model has been developed that describes the interrelating effects of plastic deformation and applied stress on hysteresis loops based on the theory of ferromagnetichysteresis. In the current model the strength of pinning sites for domain walls is characterized by the pinning coefficient keff given by keff=k0+k′σ. The term k0 depicts pinning of domain walls by dislocations and is proportional to ρn, where ρ is the number density of dislocation which is related to the amount of plastic strain, and the exponent n depends on the strength of pinning sites. The second term k′σ∝−3/2λs/2mσ, where m is magnetization and λs is magnetostriction constant, describes the changes in pinning strength on a domain wall induced by an applied stress σ. The model was capable of reproducing the stress dependence of hysteresis loop properties such as coercivity and remanence of a series of nickel samples which were pre-strained to various plastic strain levels. An empirical relation was found between the parameter k0 and the plastic strain, which can be interpreted in terms of the effects on the strength of domain wall pinning of changes in dislocation density and substructure under plastic deformation

Post-vaccine epidemiology of serotype 3 pneumococci identifies transformation inhibition through prophage-driven alteration of a non-coding RNA

Background: The respiratory pathogen Streptococcus pneumoniae (the pneumococcus) is a genetically diverse bacterium associated with over 101 immunologically distinct polysaccharide capsules (serotypes). Polysaccharide conjugate vaccines (PCVs) have successfully eliminated multiple targeted serotypes, yet the mucoid serotype 3 has persisted despite its inclusion in PCV13. This capsule type is predominantly associated with a single globally disseminated strain, GPSC12 (clonal complex 180).Methods: A genomic epidemiology study combined previous surveillance datasets of serotype 3 pneumococci to analyse the population structure, dynamics, and differences in rates of diversification within GPSC12 during the period of PCV introductions. Transcriptomic analyses, whole genome sequencing, mutagenesis, and electron microscopy were used to characterise the phenotypic impact of loci hypothesised to affect this strain's evolution.Results: GPSC12 was split into clades by a genomic analysis. Clade I, the most common, rarely underwent transformation, but was typically infected with the prophage phi OXC141. Prior to the introduction of PCV13, this Glade's composition shifted towards a phi OXC141-negative subpopulation in a systematically sampled UK collection. In the post-PCV13 era, more rapidly recombining non-Clade I isolates, also phi OXC141-negative, have risen in prevalence. The low in vitro transformation efficiency of a Clade I isolate could not be fully explained by the similar to 100-fold reduction attributable to the serotype 3 capsule. Accordingly, prophage phi OXC141 was found to modify csRNA3, a non-coding RNA that inhibits the induction of transformation. This alteration was identified in -30% of all pneumococci and was particularly common in the unusually clonal serotype 1 GPSC2 strain. RNA-seq and quantitative reverse transcriptase PCR experiments using a genetically tractable pneumococcus demonstrated the altered csRNA3 was more effective at inhibiting production of the competence-stimulating peptide pheromone. This resulted in a reduction in the induction of competence for transformation.Conclusion: This interference with the quorum sensing needed to induce competence reduces the risk of the prophage being deleted by homologous recombination. Hence the selfish prophage-driven alteration of a regulatory RNA limits cell-cell communication and horizontal gene transfer, complicating the interpretation of post-vaccine population dynamics

Application of magnetomechanical hysteresis modeling to magnetic techniques for monitoring neutron embrittlement and biaxial stress. Progress report, June 1991--December 1991

The objective is to investigate experimentally and theoretically the effects of neutron embrittlement and biaxial stress on magnetic properties in steels, using various magnetic measurement techniques. Interaction between experiment and modeling should suggest efficient magnetic measurement procedures for determining neutron embrittlement biaxial stress. This should ultimately assist in safety monitoring of nuclear power plants and of gas and oil pipelines. In the first six months of this first year study, magnetic measurements were made on steel surveillance specimens from the Indian Point 2 and D.C. Cook 2 reactors. The specimens previously had been characterized by Charpy tests after specified neutron fluences. Measurements now included: (1) hysteresis loop measurement of coercive force, permeability and remanence, (2) Barkhausen noise amplitude; and (3) higher order nonlinear harmonic analysis of a 1 Hz magnetic excitation. Very good correlation of magnetic parameters with fluence and embrittlement was found for specimens from the Indian Point 2 reactor. The D.C. Cook 2 specimens, however showed poor correlation. Possible contributing factors to this are: (1) metallurgical differences between D.C. Cook 2 and Indian Point 2 specimens; (2) statistical variations in embrittlement parameters for individual samples away from the stated men values; and (3) conversion of the D.C. Cook 2 reactor to a low leakage core configuration in the middle of the period of surveillance. Modeling using a magnetomechanical hysteresis model has begun. The modeling will first focus on why Barkhausen noise and nonlinear harmonic amplitudes appear to be better indicators of embrittlement than the hysteresis loop parameters

Expression profiling identifies genes involved in emphysema severity

Chronic obstructive pulmonary disease (COPD) is a major public health problem. The aim of this study was to identify genes involved in emphysema severity in COPD patients

The frontline antibiotic vancomycin induces a zinc starvation response in bacteria by binding to Zn(II).

Vancomycin is a front-line antibiotic used for the treatment of nosocomial infections, particularly those caused by methicillin-resistant Staphylococcus aureus. Despite its clinical importance the global effects of vancomycin exposure on bacterial physiology are poorly understood. In a previous transcriptomic analysis we identified a number of Zur regulon genes which were highly but transiently up-regulated by vancomycin in Streptomyces coelicolor. Here, we show that vancomycin also induces similar zinc homeostasis systems in a range of other bacteria and demonstrate that vancomycin binds to Zn(II) in vitro. This implies that vancomycin treatment sequesters zinc from bacterial cells thereby triggering a Zur-dependent zinc starvation response. The Kd value of the binding between vancomycin and Zn(II) was calculated using a novel fluorometric assay, and NMR was used to identify the binding site. These findings highlight a new biologically relevant aspect of the chemical property of vancomycin as a zinc chelator.This work was supported by funding from the Royal Society, UK (516002.K5877/ROG), the Medical Research Council, UK (G0700141). A.Z. was supported from the Said foundation and Cambridge Trust.This is the final version of the article. It first appeared from Nature Publishing Group via http://dx.doi.org/10.1038/srep1960