Horizontal Gene Transfer and The Evolution of Bacterial Cooperation

Bacteria frequently exhibit cooperative behaviors but cooperative strains are vulnerable to invasion by cheater strains that reap the benefits of cooperation but do not perform the cooperative behavior themselves. Bacterial genomes often contain mobile genetic elements such as plasmids. When a gene for cooperative behavior exists on a plasmid, cheaters can be forced to cooperate by infection with this plasmid, rescuing cooperation in a population in which mutation or migration has allowed cheaters to arise. Here we introduce a second plasmid that does not code for cooperation and show that the social dilemma repeats itself at the plasmid level in both within-patch and metapopulation scenarios, and under various scenarios of plasmid incompatibility. Our results suggest that although plasmid carriage of cooperative genes can provide a transient defense against defection in structured environments, plasmid and chromosomal defection remain the only stable strategies in an unstructured environment. We discuss our results in the light of recent bioinformatic evidence that cooperative genes are overrepresented on mobile elements

Navigation-by-preference: A new conversational recommender with preference-based feedback

We present Navigation-by-Preference, n-by-p, a new conversational recommender that uses what the literature calls preference-based feedback. Given a seed item, the recommender helps the user navigate through item space to find an item that aligns with her long-term preferences (revealed by her user profile) but also satisfies her ephemeral, short-term preferences (revealed by the feedback she gives during the dialog). Different from previous work on preference-based feedback, n-by-p does not assume structured item descriptions (such as sets of attribute-value pairs) but works instead in the case of unstructured item descriptions (such as sets of keywords or tags), thus extending preference-based feedback to new domains where structured item descriptions are not available. Different too is that it can be configured to ignore long-term preferences or to take them into account, to work only on positive feedback or to also use negative feedback, and to take previous rounds of feedback into account or to use just the most recent feedback. We use an offline experiment with simulated users to compare 60 configurations of n-by-p. We find that a configuration that includes long-term preferences, that uses both positive and negative feedback, and that uses previous rounds of feedback is the one with highest hit-rate. It also obtains the best survey responses and lowest measures of effort in a trial with real users that we conducted with a web-based system. Notable too is that the user trial has a novel protocol for experimenting with short-term preferences

The genetic basis of the fitness costs of antimicrobial resistance : : a meta-analysis approach

Peer reviewedPublisher PD

Read-across of 90-day rat oral repeated-dose toxicity: A case study for selected β-olefinic alcohols

There are no in vivo repeated-dose data for the vast majority of β-olefinic alcohols. However, there are robust and consistent ex vivo data suggesting many of these chemicals are metabolically transformed, especially in the liver, to reactive electrophilic toxicants which react in a mechanistically similar manner to acrolein, the reactive metabolite of 2-propen-1-ol. Hence, an evaluation was conducted to determine suitability of 2-propen-1-ol as a read-across analogue for other β-olefinic alcohols. The pivotal issue to applying read-across to the proposed category is the confirmation of the biotransformation to metabolites having the same mechanism of electrophilic reactivity, via the same metabolic pathway, with a rate of transformation sufficient to induce the same in vivo outcome. The applicability domain for this case study was limited to small (C3 to C6) primary and secondary -olefinic alcohols. Mechanistically, these -unsaturated alcohols are considered to be readily metabolised by alcohol dehydrogenase to polarised α, -unsaturated aldehydes and ketones. These metabolites are able to react via the Michael addition reaction mechanism with thiol groups in proteins resulting in cellular apoptosis and/or necrosis. The addition of the non-animal in chemico reactivity data (50% depletion of free glutathione) reduced the uncertainty so the read-across prediction for the straight-chain olefinic -unsaturated alcohols is deemed equivalent to a standard test. Specifically, the rat oral 90-day repeated-dose No Observed Adverse Effect Level (NOAEL) for 2-propen-1-ol of 6 mg/kg body weight bw/d in males based on increase in relative weight of liver and 25 mg/kg bw/d in females based on bile duct hyperplasia and periportal hepatocyte hypertrophy in the liver, is read across to fill data gaps for the straight-chained analogues

Mobile DNA can drive lineage extinction in prokaryotic populations

Natural selection ultimately acts on genes and other DNA sequences. Adaptations that are good for the gene can have adverse effects at higher levels of organization, including the individual or the population. Mobile genetic elements illustrate this principle well, because they can self-replicate within a genome at a cost to their host. As they are costly and can be transmitted horizontally, mobile elements can be seen as genomic parasites. It has been suggested that mobile elements may cause the extinction of their host populations. In organisms with very large populations, such as most bacteria, individual selection is highly effective in purging genomes of deleterious elements, suggesting that extinction is unlikely. Here we investigate the conditions under which mobile DNA can drive bacterial lineages to extinction. We use a range of epidemiological and ecological models to show that harmful mobile DNA can invade, and drive populations to extinction, provided their transmission rate is high and that mobile element-induced mortality is not too high. Population extinction becomes more likely when there are more elements in the population. Even if elements are costly, extinction can still occur because of the combined effect of horizontal gene transfer, a mortality induced by mobile elements. Our study highlights the potential of mobile DNA to be selected at the population level, as well as at the individual level

Integrative Gene Regulatory Network Analysis Reveals Light-Induced Regional Gene Expression Phase Shift Programs in the Mouse Suprachiasmatic Nucleus

We use the multigenic pattern of gene expression across suprachiasmatic nuclei (SCN) regions and time to understand the dynamics within the SCN in response to a circadian phase-resetting light pulse. Global gene expression studies of the SCN indicate that circadian functions like phase resetting are complex multigenic processes. While the molecular dynamics of phase resetting are not well understood, it is clear they involve a “functional gene expression program”, e.g., the coordinated behavior of functionally related genes in space and time. In the present study we selected a set of 89 of these functionally related genes in order to further understand this multigenic program. By use of high-throughput qPCR we studied 52 small samples taken by anatomically precise laser capture from within the core and shell SCN regions, and taken at time points with and without phase resetting light exposure. The results show striking regional differences in light response to be present in the mouse SCN. By using network-based analyses, we are able to establish a highly specific multigenic correlation between genes expressed in response to light at night and genes normally activated during the day. The light pulse triggers a complex and highly coordinated network of gene regulation. The largest differences marking neuroanatomical location are in transmitter receptors, and the largest time-dependent differences occur in clock-related genes. Nighttime phase resetting appears to recruit transcriptional regulatory processes normally active in the day. This program, or mechanism, causes the pattern of core region gene expression to transiently shift to become more like that of the shell region

The evolution of plasmid-carried antibiotic resistance

BACKGROUND: Antibiotic resistance represents a significant public health problem. When resistance genes are mobile, being carried on plasmids or phages, their spread can be greatly accelerated. Plasmids in particular have been implicated in the spread of antibiotic resistance genes. However, the selective pressures which favour plasmid-carried resistance genes have not been fully established. Here we address this issue with mathematical models of plasmid dynamics in response to different antibiotic treatment regimes. RESULTS: We show that transmission of plasmids is a key factor influencing plasmid-borne antibiotic resistance, but the dosage and interval between treatments is also important. Our results also hold when plasmids carrying the resistance gene are in competition with other plasmids that do not carry the resistance gene. By altering the interval between antibiotic treatments, and the dosage of antibiotic, we show that different treatment regimes can select for either plasmid-carried, or chromosome-carried, resistance. CONCLUSIONS: Our research addresses the effect of environmental variation on the evolution of plasmid-carried antibiotic resistance

A Whole-Cell Biosensor for Monitoring Pesticide Pollution

A novel whole-cell amperometric biosensor was developed and capable of detecting ammonium chloride, 2,4-dinitrophenol, phenol, formaldehyde, CMPP-K, chlorotoluron and simazine at the mgl-! level. The biosensor was optimised for performance in terms of the biocatalyst, the redox mediators and the biosensor construction and operation. Ninety-six micro-organisms were isolated from a random soil sample and screened for sensitivity to CMPP-K, chlorotoluron and simazine using radial diffusion plates containing the herbicide, replica plating on herbicide agar, a novel rapid inhibition growth method and changes in respiratory activity using an oxygen electrode. Nine micro-organisms were found to have properties that could be used. They were identified by standard microbiological tests (optical and scanning electron microscopy, Gram stain, catalase test, oxidase test, oxidative and fermentative activity, motility and spore stain) and by modern biochemical tests (API 20 NE strip and APi 50 CHB strip). The micro-organisms were identified as Pseudomonas fluorescens, Xanthomonas maltophilia, Acinetobacter baumannii, Bacillus cereus E, Bacillus cereus F, Bacillus £121 and Bacillus H910. Two of the Gram positive bacteria could not be identified by the API 50 CHB strip and these were named Gpnsr B12 and Gpnsr G34. All bacteria were at most members of the hazard group 2 ACDP categorisation and thus, safe to work with. A three electrode bioelectrochemical cell was constructed in the reactor configuration. Three different carbon working electrodes and four agitation devices were tested to decrease the background noise. Cyclic voltammetry was performed on nine potential redox mediators (potassium ferricyanide, resorufin, p-benzoquinone, benzy| violiogen, 2,6-dichlorophenol-indophenol, brilliant cresyl blue, phenazine ethosulphate, methylene blue and thionine) and tested with each of the nine bacteria. Three mediators (potassium ferricyanide, p-benzoquinone and 2,6-dichlorophenol-indophenol) gave responses suitable for use in the biosensor. The greatest rate of mediator reduction was achieved by optimising the mediator concentration and time of biocatalyst sampling for each microorganism. Benzoquinone exerted a toxic effect on all the bacteria except the Bacillus cereus Strains. The response of each combination of mediator and micro-organism when insulted by the pollutants was monitored using the biosensor. Measurement was based on a differential process where the rate of mediator reduction was compared before and after the addition of pollutant. Where possible, the limit of detection and concentration that caused either a 50% or 25% change in mediator reduction was calculated. Permeability of the bacteria was artificially increased using either a lysozyme-EDTA preparation or | % (v/v) Tween 20. This treatment had the effect of increasing mediator reduction by some bacteria and decreasing mediator reduction by others. Several bacteria had increased sensitivity to the herbicides following permeation. The responses of the bacteria to herbicides when monitored by respiratory activity measured on the oxygen electrode presented the possibility of distinguishing one herbicide from the other three herbicides. This was also possible using the mediated amperometric biosensor but much more complex

Redundant Actuation of Twisted and Coiled Polymer Muscles to Improve Tracking Performance

Twisted and coiled polymer muscles (TCPMs) are a type of artificial muscle with a remarkable power-to-weight ratio. However, actuation dynamics are slow compared to other artificial muscles. This work aims to improve dynamic performance by incorporating redundancy. Specifically, this work examines if TCPM bundles of heterogeneous geometries containing high-force low-bandwidth actuators and low-force high-bandwidth actuators have a substantially better tracking performance than that of bundles of homogeneous geometries. First, a white-box model was created to simulate TCPM dynamics as a function of geometric parameters. The model revealed fiber diameter is the only geometric parameter that represents a trade-off between TCPM bandwidth and maximum realizable force for isometric force tracking. Next, an optimum feedforward controller was designed to distribute the reference among redundant actuators. Finally, a brute-force optimization was conducted to find the optimum configurations of heterogeneous and homogeneous TCPM bundles and the associated tracking performances. Optimal homogeneous configurations outperformed all heterogeneous configurations irrespective of number of TCPMs in parallel or reference signal. For unidirectional configurations, a nontrivial fiber diameter optimizes tracking performance. For antagonistic configurations, tracking performance improves monotonically with increasing fiber diameter