Non-genetic mechanisms communicating antibiotic resistance:rethinking strategies for antimicrobial drug design

Introduction: Infections by multidrug-resistant bacteria are of great concern worldwide. In many cases, resistance is not due to the presence of specific antibiotic-modifying enzymes, but rather associated with a general impermeability of the bacterial cell envelope. The molecular bases of this intrinsic resistance are not completely understood. Moreover, horizontal gene transfers cannot solely explain the spread of intrinsic resistance among bacterial strains. Areas covered: This review focuses on the increased intrinsic antibiotic resistance mediated by small molecules. These small molecules can either be secreted from bacterial cells of the same or different species (e.g., indole, polyamines, ammonia, and the Pseudomonas quinolone signal) or be present in the bacterial cell milieu, whether in the environment, such as indole acetic acid and other plant hormones, or in human tissues and body fluids, such as polyamines. These molecules are metabolic byproducts that act as infochemicals and modulate bacterial responses toward antibiotics leading to increasing or decreasing resistance levels. Expert opinion: The non-genetic mechanisms of antibiotic response modulation and communication discussed in this review should reorient our thinking of the mechanisms of intrinsic resistance to antibiotics and its spread across bacterial cell populations. The identification of chemical signals mediating increased intrinsic antibiotic resistance will expose novel critical targets for the development of new antimicrobial strategies.

Timekeeping strategies operate independently from spatial and accuracy demands in beat-interception movements

The prevailing paradigm for researching sensorimotor synchronisation in humans involves finger tapping and temporal accuracy measures. However, many successful sensorimotor synchronisation actions require not only to be 'in time', but also to be in a predefined spatial position. Reaching this spatial position in many everyday actions often exceeds the average amplitude of a finger movement. The aim of this study is to address how people coordinate their movement to be in the right place at the right time when the scale of the movement varies. Does the scale of the movement and accuracy demands of the movement change the ability to accurately synchronise? To address these questions, a sensorimotor synchronisation task with three different inter-beat intervals, two different movement amplitudes and two different target widths was used. Our experiment demonstrated that people use different timing strategies-employing either a movement strategy (varying movement time) or a waiting strategy (keeping movement time constant) for large-scale movements. Those two strategies were found to be equally successful in terms of temporal accuracy and variability (spread of errors). With longer interval durations (2.5 and 3.5 s), variability of sensorimotor synchronisation performance increased (measured as the spread of errors). Analysing the data using the Vorberg and Wing (Handbook of perception and action. Academic Press, New York, pp 181-262, 1996) model shows a need to develop further existing timing models of sensorimotor synchronisation so that they could apply to large-scale movements, where different movement strategies naturally emerge.

Animal foraging from an individual perspective: an object orientated model

A model system, HOOFS (Hierarchical Object Orientated Foraging Simulator), has been developed to study foraging by animals in a complex environment. The model is implemented using an individual-based object-orientated structure. Different species of animals inherit their general properties from a generic animal object which inherits from the basic dynamic object class. Each dynamic object is a separate program thread under the control of a central scheduler. The environment is described as a map of small hexagonal patches, each with their own level of resources and a patch-specific rate of resource replenishment. Each group of seven patches (0th order) is grouped into a Ist order super-patch with seven nth order super-patches making up a n + 1th order super-patch for n up to a specified value. At any time each animal is associated with a single patch. Patch choice is made by combining the information on the resources available within different order patches and super-patches along with information on the spatial location of other animals. The degree of sociality of an animal is defined in terms of optimal spacing from other animals and by the weighting of patch choice based on social factors relative to that based on food availability. Information, available to each animal, about patch resources diminishes with distance from that patch. The model has been used to demonstrate that social interactions can constrain patch choice and result in a short-term reduction of intake and a greater degree of variability in the level of resources in patches. We used the model to show that the effect of this variability on the animal's intake depends on the pattern of patch replenishment. (C) 1998 Elsevier Science B.V. All rights reserved.</p>

Convergent evolutionary processes driven by foraging opportunity in two sympatric morph pairs of Arctic charr with contrasting post-glacial origins

The expression of two or more discrete phenotypes amongst individuals within a species (morphs) provides multiple modes upon which selection can act semi-independently, and thus may be an important stage in speciation. In the present study, we compared two sympatric morph systems aiming to address hypotheses related to their evolutionary origin. Arctic charr in sympatry in Loch Tay, Scotland, exhibit one of two discrete, alternative body size phenotypes at maturity (large or small body size). Arctic charr in Loch Awe segregate into two temporally segregated spawning groups (breeding in either spring or autumn). Mitochondrial DNA restriction fragment length polymorphism analysis showed that the morph pairs in both lakes comprise separate gene pools, although segregation of the Loch Awe morphs is more subtle than that of Loch Tay. We conclude that the Loch Awe morphs diverged in situ (within the lake), whereas Loch Tay morphs most likely arose through multiple invasions by different ancestral groups that segregated before post-glacial invasion (i.e. in allopatry). Both morph pairs showed clear trophic segregation between planktonic and benthic resources (measured by stable isotope analysis) but this was significantly less distinct in Loch Tay than in Loch Awe. By contrast, both inter-morph morphological and life-history differences were more subtle in Loch Awe than in Loch Tay. The strong ecological but relatively weak morphological and life-history divergence of the in situ derived morphs compared to morphs with allopatric origins indicates a strong link between early ecological and subsequent genetic divergence of sympatric origin emerging species pairs. The emergence of parallel specialisms despite distinct genetic origins of these morph pairs suggests that the effect of available foraging opportunities may be at least as important as genetic origin in structuring sympatric divergence in post-glacial fishes with high levels of phenotypic plasticity. (c) 2012 The Linnean Society of London, Biological Journal of the Linnean Society, 2012, , .

Emergence time and foraging activity in Pallas' mastiff bat, Molossus molossus (Chiroptera: Molossidae) in relation to sunset/sunrise and phase of the moon

The decision on when to emerge from the safety of a roost and forage for prey is thought to be a result of the trade off between peak insect abundance and predation pressure for bats. In this study we show that the velvety free-tailed bat Molossus molossus emerges just after sunset and just before sunrise for very short foraging bouts (average 82.2 min foraging per night). Contrary to previous studies, bats remain inactive in their roost between activity patterns. Activity was measured over two complete lunar cycles and there was no indication that phase of the moon had an influence on emergence time or the numbers of bats that emerged from the roost. This data suggests that M. molossus represents an example of an aerial hawking bat whose foraging behaviour is in fact adapted to the compromise between the need to exploit highest prey availability and the need to avoid predation.

Foraging-farming transitions at the Niah Caves, Sarawak, Borneo

The Niah Caves in Sarawak, Borneo, have captured evidence for people and economies of 8000 and 4000 years ago. Although not continuous on this site, these open two windows on to life at the cultural turning point, broadly equivalent to the transition from Mesolithic to Neolithic. They have much in common, inferring that the occupants, perhaps belonging to an older maritime dispersal, had a choosy appetite for the Neolithic package.

Web-based social movements contesting marketing strategy: Mobilization of multiple actors and rhetorical strategies

Previous studies suggest that marketing strategy is developed and used to mobilise and configure the actions of firm actors, creating a set of stabilising activities focused on the firm–customer dyad. Destabilising forces precipitated by the Internet and associated digital technologies involving contention and disruption by multiple actors are much less prevalent in the marketing literature. The central point we advance is that rather than marketing strategy being a controlled and stabilising force for firms in their relationships with customers, it can often lead to socially produced spaces where consumers and, importantly, other multiple actors form a social movement to actively attempt to destabilise it and contest its legitimacy. Using an innovative research approach, the findings of this study show how social movements proactively enrol and mobilise a wide range of relevant actors into a network of influence. Critical to this are rhetorical strategies, acting as important levers in attempts to destabilise and delegitimise a dominant firm's marketing strategy.

Treatment of lung infection in patients with cystic fibrosis:Current and future strategies

In patients with cystic fibrosis (CF) lung damage secondary to chronic infection is the main cause of death. Treatment of lung disease to reduce the impact of infection, inflammation and subsequent lung injury is therefore of major importance. Here we discuss the present status of antibiotic therapy for the major pathogens in CF airways, including prophylaxis against infection, eradication of early infection, suppression of chronic infection, and the treatment of infective exacerbations. We outline measures to optimize maintenance treatment for infection in the light of novel antibiotic drug formulations. We discuss new developments in culture-independent microbiological diagnostic techniques and the use of tools for monitoring the success of antibiotic treatment courses. Finally, cost-effectiveness analyses for antibiotic treatment in CF patients are discussed.